Discovering biology in a digital world (Archives)

Attention new iFinch users! Turn on your data processor!

2008-10-17T14:44:00.000-07:00

New iFinch users:

Before you can upload data, you will need to turn on your data processor.

Checking and starting your Finch data processor

1. Log into your iFinch account.

2. Find and select the Data Processor link in the System menu.

3. Look at the Data processor status.

4. If the Data processor has stopped, you will need to Restart it by selecting the Restart button. If you are a student, you will need to have an instructor log in and do this.

Hello Kitty! or Don't Eat Me, I Study Genetics!

2006-06-30T17:00:00.000-07:00

Genetics textbooks abound with stories of European royalty and the hazards of having children after you've married one of your cousins. It struck me as an interesting parallel that the lion is such a popular symbol in so many royal coats of arms. Like the royal families of Europe, certain lion populations have also suffered from a few too many copies of certain recessive genes.

Read the rest at the new site>>

technorati tags: cats, panthers, conservation biology, biology, genetics, population genetics, DNA

My new address

2006-06-09T09:28:00.000-07:00

As Bora Zovkovic, so kindly puts it, in The Magic School Bus, summer is starting and many of us are going to SEED. Hopefully, our readers don't have too many allergies.

I will leave archives here, but you can find new postings at: http://www.scienceblogs.com/digitalbio

Time to fly

2006-05-24T10:08:00.000-07:00

"I'm goin' where the sun keeps shinin'
Thru the pourin' rain,
Goin' where the weather suits my clothes.

Bankin' off the northeast wind,
Sailin' on a summer breeze,
Skippin' over the ocean like a stone."

- Fred Neil
Everybody's Talkin (Echoes)

Where am I going?

California?

Well, there too, for a few days, but blogwise, I'm going to ScienceBlogs. And you're welcome to come visit. My new link won't be functional for a few days yet, but I will post it when I'm ready for visitors.

Subject: Announcements

Tangled Bank #54 is up and ready

2006-05-24T05:32:00.000-07:00

Yet another great collection of science blogamainia is live and ready at Science and Politics.

Hosted by Bora Zivkovic, a hard-writing science blogger extraordinare, it's Tangled Bank #54!!

Clear some time off your schedule and grab a cup of coffee, there's lots of good reading ahead.

technorati tags: carnivals, Tangled Bank, science

Hurrah for Syttende Mai!

2006-05-17T15:13:00.000-07:00

Hard-working birds on Mother's Day

2006-05-14T10:18:00.000-07:00

At first, we thought the tent caterpillars were back for the summer.

Then, we saw a bird go into the "tent."

I guess you don't get Mother's Day off until after you've laid your eggs.

Happy Mother's Day to mothers and future mothers.

Subject: Birds

technorati tags: biology, birds

Part II. Future Shock and Selenocysteine: it's time again to update the databanks

2006-05-11T10:16:00.000-07:00

One of the surprises (for me anyway) in discovering the existence of selenocysteine (Part I. Future Shock and Selenocysteine), was the corresponding discovery that it's encoded by UGA. Ordinarily, UGA is a stop codon. If a UGA is in an mRNA sequence, it tells the ribosome that the job is done. It's time to pack up all the tRNAs and elongation factors and move on to the next project.

But in the case of selenocysteine, we have a "work-around." Sometimes UGA stops everything, sometimes the UGA says "put the selenocysteine right here." (Someone in the office joked that the ID g-o-d must be a programmer since he/she is trying to fix bugs.)

How do the ribosomes and tRNAs know whether to stop or go?

They feel the difference.

Seriously, the sequences at the 3' end of an mRNA fold into a special hairpin shape like the one shown here (1, 2, 3). In bacteria, this structure is called a "selenocysteine insertion sequence" or SECIS element. Eucaryotes have similar structures at the 3' ends of mRNAs for selenoproteins.

The RNA in the picture has a rainbow coloring scheme (Red, Orange, Yellow, Green, Blue, Indigo, Violet). Nucleotides at the 5' end are red, nucleotides at the 3' end are violet. You can follow the colors in the RNA backbone to see how the RNA is twisted around into a hairpin shape.

One of the tests that we used to give job applicants was to have them write a short script for translating a DNA sequence in 6 reading frames. We would give them a mouse pad with the genetic code and put them to work.

Selenocysteine makes this problem a whole lot harder.

Since the recognition feature is a secondary structure, locating the coding sequences for selenocysteines presents an interesting challenge to computational biologists. Finding these sequences requires a bit more than a regular expression.

Kryukov, et. al. describe an algorithm for doing this type of search (1). They've refined it in the years since this publication, but it seems that the information has yet to percolate through much of the world's bioinformatics community.

And here, I thought I was the only one who seemed to have missed this.

Nope.

Can we find selenocysteine in GenBank?
I started to wonder if the news about selenocysteine had trickled out beyond PubMed articles and into the rest of the NCBI.

Could I find selenoprotein sequences in the Gene database? I thought this would be a good place to start since the data are well curated and there are links to reference protein sequences.

I searched and searched, and lo and behold, I found them.

The sequence above codes for human selenoprotein P. U is the one letter symbol that represents selenocysteine. This protein contains an unusually large number of selenocysteines.

I only looked at a few of the reference protein sequences (labeled NP---) from the Gene database, but they all seemed to have selenocysteines.

So the NCBI Gene Database seems to be caught up, at least for the sequences that I checked out.

Mischief and Misannotations
I followed the links to the Conserved Domain Database. (I'm writing a book on this BTW, and the CDD is really, really cool).

When I got to a summary page, I choose the SelP_C domain (since more U's are on that side of the protein). This gave me a page with a Pfam alignment between my human SelP sequence and some sequences that were chosen for Pfam. (you can take a look at this yourself by clicking the link above. Change the format to Hypertext and click Show Alignment to see the selenocysteines in the query sequence).

Reading downward, the Pfam sequences, in the alignment below, are from cow, my query(human), rat, another human sequence, and zebrafish.

Every time my query sequence has a "U," the other sequences have a "c" (purple boxes above).

This is interesting and odd. Only one of the proteins with the conserved SelP domain has selenocysteine (and it's our human query sequence).

One interpretation that Kryukov suggested in 2003 (1), (and later regretted, I'm sure), is that through evolution, cysteine was substituted for selenocysteine in organisms like the rat and mouse.

I think the presence of the other human SelP sequence argues for another interpretation, especially since it's an older version of our query.

If we click the gi links to see the database records, we find something else that's interesting.

A note in the first sequence, from the cow, deposited in April 2006, shows that someone knew about the selenocysteines,

[MISCELLANEOUS] The selenocysteines are all encoded by the opal codon, UGA.

But apparently, no one bothered to put them in the amino acid sequence, since there aren't any selenocysteines there.

Maybe they didn't read the note.

Stranger, yet, the missing selenocysteines could be rationalized away by arguing that the protein sequence is just a conceptual translation - that is, it was determined by using the standard genetic code. Except that using the standard genetic code would have generated a much shorter sequence since UGA makes translation stop. So, instead of putting in the correct amino acid, the curators (Swiss prot?) typed in the wrong amino acid. Instead of using the U for selenocysteine, they typed a C for cysteine.

The rat sequence was also updated in April 2006 and we can see that the positions of selenocysteines also seem to be marked in the GenPept record (below), but, funny, there aren't any selenocysteines in the rat sequence.

The other human sequence for SelP and the zebrafish sequence show the same kinds of annotations. Yet neither one contains selenocysteines in the amino acid sequence.

Could the source of the sequences (Pfam) be the source of the problems?
I'm not sure where the problem originates but if I search the Pfam database at the Sanger Center, for selenocysteine, I get a list of 31 proteins that contain it, and again, I get an annotation that indicates that someone is aware of selenocysteine.

SelP is the only known eukaryotic selenoprotein that contains multiple selenocysteine (Sec) residues...

Yet when I do a seed alignment, none of the amino acid sequences contain selenocysteine. Here is one example:

SEPP1_HUMAN/22-250 QDQSSLCKQPPAWSIRDQDPMLNSNGSVTVVALLQASCYLCIL
QASKLEDLRVKLKKEGYSNISYIVVNHQGISSRLKYT

The selenocysteines are missing here, too.

If I take this sequence and do a blastp search at the NCBI, I get quite few perfect matches. Just like Pfam, there are sequences in GenBank that are not yet fixed.

What is our take home message?
The simple take-home message, of course, is to be aware the FASTA sequences for selenium-containing proteins are likely to be wrong. If the annotations say there should be selenocysteine and you can't find a "u" in the sequence, it probably hasn't been fixed yet. Those of us who use the date must always be skeptical and read the literature.

The second take-home message concerns process. The acceptance of new ideas in science generally prompts some re-evaluation of older ideas. We evaluate older concepts more critically in the electric light of new ideas. It would be helpful if these processes could be applied more quickly to sequence data and bioinformatics algorithms. These results support the need for scientific curators who can read the literature, add annotations, and even make corrections in amino acid sequences, from time to time.

The amino acid matrices that we use for protein comparisons, were updated when more sequences became available for doing alignments. We all switched from using PAM to BLOSUM matrices. Maybe it's time to make update the Pfam domains as well.

Selenocysteine exists.

It's time to deal with it and get on with the work.

References:
1. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN. 2003. Characterization of mammalian selenoproteomes.
Science. 300:1439-43.

2. Diamond, AM. 2004. On the road to selenocysteine. Proc Natl Acad Sci U S A. 101: 13395-13396.

3. Yoshizawa S, Rasubala L, Ose T, Kohda D, Fourmy D, Maenaka K. 2005. Structural basis for mRNA recognition by elongation factor SelB. Nat Struct Mol Biol. 12:198-203.

Subject: Doing biology with bioinformatics

technorati tags: bioinformatics, selenocysteine, biochemistry, biology, blast, genetics, genomics, DNA, RNA, Science Education

Carnival time

2006-05-11T05:35:00.000-07:00

The carnivals are up and running.

Tangled Bank 53: Go climb a tree! looks at the tree of life from a higher point of view.

I and the bird #23 at birdDC asks the question, is it possible to do birding on the internet?

Enjoy!

Part I: Future Shock and Selenocysteine

2006-05-10T10:54:00.000-07:00

Future Shock

When I was in high school, we read an intriguing book by Alvin Toffler called "Future Shock."

Now, the book is over 30 years old but some of the predictions Toffler made were uncanny.

One of the ideas Toffler proposed was that people could become overwhelmed and disoriented with the onslaught of new information. My field is a good example. For Geospiza, helping people manage large amounts of new data, while maintaining the old, is our whole raison d’être.

But going back to Toffler, he predicted that the increasing rate of societal change would cause some people to experience symptoms of "Future Shock." One morning you might wake up in a familiar place, but everything would seem a bit different and strange. I'm channeling the ghost of Jim Morrison a bit, but the The Doors had the feeling nailed down.

It's never bothered me though, until the other day.

I learned something new that shook one of my core beliefs.

We have a new amino acid in the genetic code.

Sure, go ahead and laugh.

This might seem like an odd thing to be bothered by, but the genetic code was solved in the early 60's. Some things in life are NOT supposed to change. Yeah, there are some variations in translating DNA from different species, and we expect to learn new things from deciphering the genome, but no one expects changes in something as fundamental as the genetic code.

So, it was a bit jarring to find out that now there are 21 amino acids.

And it was even a little reasurring that no one believed me.

My husband kept insisting that this was a post-translational modification or some strange anomaly from archeabacteria.

Naturally, I was forced to hunt down a bunch of abstracts and read them to everyone (I love PubMed!).

Selenocysteine: our 21st amino acid

It's true. The new amino acid is selenocysteine and there are even special tRNAs that can add it during translation. The translation machinary recognizes the UGA stop codon, plus special secondary structures in mRNA, and puts in a selenocysteine instead of stopping.

This amino acid is uncommon, but GenBank has 7904 entries for selenoproteins and 3293 RefSeqs. Many are probably orthologs (the same protein in different organisms) or our favorites, those wonderful "hypothetical proteins," and I think some of the records represent the same sequence, but there's still a fair number to be found (except in Pfam, but more on that in part II).

Selenoproteins are pretty wide-spread, too. At least 25 selenoproteins are known in humans and I found papers describing them in mouse, fruit flies, humans, fish, bacteria, and protozoans. Most selenoproteins only contain one selenium and it's positioned at the active site. One selenoprotein contains so many seleniums that this one protein, alone, accounts for half of the selenium in a cell.

I'm not too sure yet, about the function of these proteins. Some of the selenoproteins may be important in redox reactions, one might prevent heavy metal toxicity, and there seems to be some link to cancer, too.

And, guess what?

I'm wasn't the only one who was taken by surprise. It looks like some of our favorite bioinformaticists and genome annotators missed this one, too.

Stay tuned.

In part II, we look at the infinite loop of information updates and an interesting conclusion drawn from erroneous annotations.

Subject: Doing biology with bioinformatics

technorati tags: biology, bioinformatics, blast, genetics, genomics, DNA, RNA, Science Education

Animalcules Volume 1, Issue 7

2006-05-03T19:32:00.000-07:00

It's the 4th of May, almost summer time and time to think about microbes.

Some of them are giant, some are just, well, ... unusual.

I guess we'll let the procaryotes go first, since apparently they're working by the clock. And you probably thought it was simple being a single-celled organism without a nucleus. You can read about them in Clocks in Bacteria IV: Clocks in other bacteria, brought to you by none other than Circadiana.

Next, in keeping with the image of pathogens as giant fluffy toys, we have a collection of Hands-on, Fun Microbiology Activities from the ASM. Let's Get Small, Yeast on the Rise, and Fun with Fomites are some of the entertaining activities that you could either try at home, or use to liven up a class with the small fry, or even larger fry. Fun with Fomites exams the wonders of things that grow on your kitchen cutting board, or even the pennies in your pockets. And there are plenty of helpful suggestions for the cognitively impaired, but since this isn't a political sort of blog, I won't go there.

Do your bacteria keep swimming away? Isn't chemotaxis a pain? I remember when researchers studied flagella and bacterial motion by using anti-flagella antibodies to pin the little suckers to a slide and then, they would watch the bacteria twirl around and around with a microscope. Ah, torturing bacteria! The BioCurious have found a better way. "Studying Bacteria with Atomic Force Microscopy" looks far more fun than old antibody and slide method.

Further representing the uncultured world, we have the GMO pundit asking, 'Is Studying Soil DNA Any Value to The Australian Farmer Part 1. About 99% of soil bacteria have never been grown." Even if they're not, my collaborators have got college biology students doing PCR and sequencing dirt, so the farmers may not care, but knowing your soil bacteria, will still be important for getting a good grade in general biology.

In the Deep-Sea News, we learn about some lovely cyanobacteria, the Deep phytoplankter Prochlorococcus, a "plain little mite at first site" but very productive in terms of biomass.

Ewen Callaway from Complex Medium contemplates the true meaning of diversity, in Does microbial diversity count? Is is important to preserve the bacteria in a desert oasis?

A carnival with bacteria, of course, would never be complete without our faithful laboratory, friend, the mouse of the microbes, the king of our colon, the one and many, E. coli. In E. coli, Shigella, and Creationism, Mike the Mad Biologist even manages to link our fuzzy friend to creationism and Shigella, with an amazing amount of intestinal fortitude.

Now, Mike the Mad also has me worried about cleaning my aquarium. He writes More on That NY Times Article about the dangers of getting Salmonella from your fish tank. And, if that wasn't enough, well, he explains why tummy aches in Australia (Australia, Agriculture, and Antibiotics) might last longer than you'd think.

Who knows what evil bacteria lurk in the hearts of men? The protozoa know. Inspired by the TV, Paul Orwin identifies a microbial influence on pop culture (Microbiology and Pop Culture).

So far, we've let procaryotes have all the fun. This bird has had enough. Maybe it smelled the Campybacter. Or could it be that this chicken has read Emerging Disease and Zoonoses #13--new swine influenza virus detected and just wants to play it safe? Maybe this rooster watched this short hysterically funny video clip and just isn't willing to play chicken?

Before we go too mad, perhaps we should foam at the mouth to read this story, and accompanying links on Rabies, the Novel, from Bora Zivkovic of Science and Politics.

And for one last, truly viral article, lets contemplate our friend the mosquito, one last whiny time, and read about West Nile Virus, a last friendly parting thought, from our friends at MicrobeWorld.

Check out the schedule for the next episode of Animalcules!

Subject: Microbiology

technorati tags:
animalcules, biology, DNA, genomics, microbiology
science education

Powers of Ten and Shifting Perspectives on Science and Society

2006-04-28T08:17:00.000-07:00

I bought this book for my kids awhile back, called "Powers of Ten" by Philip Morrison and Phylis Morrison. The premise (quoted from Amazon) is this:

"Starting with a view of a billion light-years, the book (like the film) moves inward, with each page being at one-tenth the scale of the previous one. In 25 steps, you're looking at a picnic by the shores of Lake Michigan, then plunging into a human hand, down through the cells inside it, the DNA inside the cells, the atoms inside the DNA, and the subatomic particles inside the atom. By the time you've gone a total of 40 steps, you're in a world of quantum uncertainty."

Each shift in perspective changes the view as familiar objects are seen in new ways.

My life has done the same thing, except in the opposite direction. For the first 25 years or so, my perspective was from the nuclear level as all the electrons revolved around me. And I would have completely agreed with these opinions in the comments at Epigenetics News:

"I did get a discussion about this topic going in the lab today (three postdocs, a tenured faculty member and a couple of other students). Surprisingly, there was very little sympathy for the high school students seeking biotech internships. The general consensus was that even if a student was taken on as an intern during the summer, it would take so much time to “get them up to speed” without any background knowledge coming in (and potentially no experience working a real job at all) that it just wouldn’t be worth the effort."

As a 25 yr old graduate student, I still would have agreed.

I had to TA during the entire first year of graduate school and I didn't particularly like it. Why should I work hard as a TA when I had my own research to do and courses to pass? Why lose my valuable research time? Why bother? It wasn't my fault that students who were seniors in college couldn't do the basic algebra we asked for in our microbiology course.

Let's fast-forward five more years to age thirty.

Now, I'm a post-doc with a baby who goes to day-care. My non-profit research institution holds Monday afternoon post-doc research seminars at 5:15 pm that last until 6:30. But my day care provider requires that children be picked up at 5:00 pm, and since I'm making $17,000 a year as a post-doc, and my husband is a grad student, we only have one car (which I drive). So I go to the scientist in charge of the weekly seminar and ask if we can move the time, only to be told "no one else considers this to be a problem." Oooh, that was a jarring shift in perspective. Maybe the nuclear model has to be replaced. I advance grimly to the cellular level.

Five years later, my perspective shifted farther outward to the organism view. And I still would have agreed with the lab in Epigenetics News. Why have high school students in the lab? What could they do?

I'm teaching in a community college. I'm about the same age as many of my students (the median age is 33), and I've gone from wondering why anyone would hire a community college student to wondering why they wouldn't. I've watched community college students, many with bachelor's degrees, some with kids, go to school full-time, and work at both jobs and internships, sometimes simultaneously. And I have developed a whole new level of respect and awe for what people can do.

I've also learned about multiple intelligences. Students can get A's on every assignment and write brilliant essays on exams and set boxes of Kimwipes on fire when they get a job in a lab. There are plenty of opposites, too, like the students who get C's on every test and become highly-valued technicians or even go on to graduate school. One of my former students, with only a two-year degree, gave a key note talk at cytokine conference and one student started his own biotech company.

Well, here we are, ten years later, and I'm starting see the world from the ecosystem perspective. I work at a bioinformatics company and have one child in high school and one in middle school. I know now, how efficiently the public school system - at least middle school - turns kids off of science early on. I no longer think that we can afford to wait until college - or in the case of community colleges - after college - to counteract the impressions that kids get of science and scientists.

Not only have I come to appreciate the broad spectrum of capabilities that high school students represent, but I can stand back, now, and see other goals beyond getting a nice-looking gel or cloning that fragment of DNA.

Why do I think it's important to find science opportunities for high school students and undergraduates?

There are many reasons. But looking from an ecosystem view, internships are one way to help society achieve the goals to which many scientists give lip service and some even work to support. These are goals like a scientifically literate society, a diverse society, and a society that doesn't view science as an elitist enterprise that's only open to rich white kids. Because, like it or not, that is how the outside world views the academy.

If we had a scientifically literate society we would be working on serious issues like global warming and over-fishing and disappearing species. We wouldn't have to waste our time with silly distractions like intelligent design. I don't think there would be such an anti-science sentiment on the part of the general public (1) if it were understood that strong science empowers all of us.

Of course, neither University research labs nor biotech companies are or should be charities, and my experience has been that they can't be relied on to act in a consistently charitable manner, anyway. If we are to increase diversity in science and develop a scientifically literate society, we need a workable way to open the laboratory doors and let in more students.

References:
1. Liza Gross. 2006.Scientific Illiteracy and the Partisan Takeover of Biology.PLoS Biol 4(5): e167.

Subject: Education

technorati tags: biotechnology,
teaching-carnival
education
science education

Spring is in the heron

2006-04-27T06:02:00.000-07:00

The herons have all built their nests now and are happily sitting on them. It seemed like a good time to post some pictures from the early days of nest repair.

It's a little hard to tell but this bird is carrying a stick and coming in for a landing as you can see below.

Even herons have to take a break from nest building sometimes.

What if we built a zoo and the animals just happened to show up? This heron did exactly that. It's sitting in the penguin exhibit at the Woodland Park Zoo enjoying the abundant little fish.

Everyone else enjoyed watching the heron. It's a good thing herons can't read.

Subject: Birds

technorati tags: biology, birds

Carnivals, Carnivals, and more Carnivals

2006-04-26T06:17:00.000-07:00

A long, long, time ago, in a galaxy far, far away there came ....(pause for dramatic effect)

TANGLED BANK #52

And I've been promoted to Jedi trainer! Be sure to clear some time for some enjoyable reading.

In keeping with my new role as Jedi trainer, you might also want to check out the Education Carnival over at Education Wonk.

Re-thinking biotech student internships, part II

2006-04-24T09:53:00.000-07:00

Three models for getting lab experience

In part I, I wrote about the need for both high school and college students to have learning experiences outside of school. High school students need learning experiences that open their eyes to potential careers and help them focus on education. College students need learning experiences that will open doors to jobs. Internships meet the needs of both groups but biotech companies only offer a small number of internships, if they offer any at all.

I've now seen three different models that present interesting, and viable alternatives to the traditional view of company internships. Each model allows students to gain hands-on working experience in a company or company-like setting. And the beauty is that, in contrast to the standard practice, none of these models depends on the benevolence or transient charity of local companies.

How do you create opportunities for students to do internships?

Model 1. Make your school program more like a research lab

This model is exemplified by the biotech program at Bates Technical College in Tacoma. At Bates, Students can start the biotech program on any given Monday and continue until they're finished. I've known about the school for a long time, but I never understood how this worked until I heard the director, Kelly Hamilton, talk at a Bio-Link conference last week. Apparently, this model works more like an apprenticeship or graduate school. Students join the program, get a customized training plan and get right to work in the lab. I don't think the Bates program entirely substitutes for a company internship, but Bates students do develop solid lab skills since they spend a considerable amount time working independently in the lab.

Model 2. Become an incubator

Shoreline Community College has become an incubator. Xactagen, a small biotech company, has moved in and shares some of Shoreline's lab facilities. This is truly a win-win situation. The company benefits from the infrastructure at the community college and the college benefits from the interaction between students and Xactagen employees. Having an authentic research program happening on site makes biotech lab a familiar site and Xactagen employees serve as informal instructors and role models. Xactagen has also hired graduates of the SCC biotech program and has students interns employed on their projects. The benefits are many. The greatest downside is that Xactagen is too small to hire very many student interns and those interns are all college students.

Model 3. Start a contract-research company

This model is the most intriguing and, I think, shows the most promise. Community colleges have always operated small businesses as way to educating students in both running a business and different types of careers. Some of the examples at my former school were culinary arts programs where the program operates restaurants, optician-training programs, beauty salons, and day-care facilities. So, I'm really glad these ideas are finally getting tested in the realm of biotechnology.

Why not have a small college-based business that does a bit of contract research?

Dr. Tamara Goetz at Salt Lake City Community College is giving this model a try. Frustrated with the challenges of finding student internships, Dr. Goetz started InnovaBio.

InnovaBio is a small non-profit company that does contract research for biotech and nutraceutical companies in the Salt Lake area. InnovaBio has a few paid employees, acting as supervisors, but most of the lab work is done by high school and college interns. InnovaBio provides a low-risk opportunity for companies to try out high-risk products and train future employees at the same time. Further, this is a model that can handle large numbers of students and can accommodate high school students. Students can even work in non-lab areas of biotechnology, such as marketing and business development.

This is a model that should be replicated.

With all the challenges that our local high school programs and colleges face in locating student internships, and all the challenges that our local biotech industry has in finding qualified employees, I hope the educators in our state will look a bit eastward and pay attention to what's happening in Utah.

Subject: Education

technorati tags: biotechnology,
teaching-carnival
education,science education

Upcoming carnivals

2006-04-23T17:23:00.000-07:00

This is a reminder. Animalcules will be here on May 4th. If you write about tiny things (life forms that is), this is the place to show off your writings. Send Animalcule submissions to sandy at geospiza dot com with Animalcules in the subject line.

If you're not sure what an Animalcule carnival might look like like - you can take a look at the last one at the Biotech Weblog.

And the next Tangled Bank will be April 26th at The Inoculated Mind. Send those submissions to karl AT inoculatedmind DOT com and put "Tangled Bank Submission" in the subject line.

TTFN!

Re-thinking biotech student internships, part I

2006-04-22T11:37:00.000-07:00

Jobs can be learning experiences, too

I read an amusing story yesterday about a summer job packaging ice in plastic bags. I had jobs like that, too, when I was in high school. I waited tables, sold popcorn at a theatre, sold plants at a garden store, and did lots of babysitting. I learned something from every mindless part-time job, but mostly I learned that I didn't want to do them.

So when I started college, I started looking for jobs that would do more than pay the rent. I wanted first-hand impressions of potential careers. As a receptionist in a veterinarian's office, I learned that small animal vets needed to be good with handling animals and even better with handling people. As an autopsy assistant, I learned about anatomy and pathology. Working as a phlebotomist in a plasma center, I learned to spot needle tracks and find good veins. My medley of part-time and volunteer jobs were eye-opening forays into the working world.

The job that I wanted the most though, was the hardest to get. I really wanted to work in a science lab. Every now and then I would go to the student employment center and look at the job postings, but I was never eligible. The lab positions at my University required either work-study funding or work experience and I had neither. This was before the age of biotech, but I spent five years looking, and didn't find a lab job until the middle of my senior year in college.

Learning about careers

Making career choices as a young person is a challenge. It's hard to commit to a future and focus on education when you don't have a clue what a future job might involve. Some students never even consider that studying science could lead to an interesting job. They think that you need a Ph.D. or they get the interesting notion (that I heard from one of my kids) that science would be a really boring job because all you did in middle-school science class was read textbooks.

The part-time jobs that I collected were pivotal in helping me decide what I wanted to do and why I wanted to do it. For me, working as a lab technician convinced me to go on to graduate school and study science more seriously.

Over the years there has been a greater and greater push, at least in our area, to find internships in science labs for both high school and college students. Teachers want their students to know that people of all sexes, shapes, colors, and sizes work in biotech companies and that studying science can lead to an interesting career.

At the same time, internships in the biotech industry have become harder to get (especially for high school students!). As the local industry has shifted from research to production, the environment has become more controlled and closely regulated. Even though some business leaders might recognize the long-term benefits of contributing to a scientifically literate society, and inspiring future employees, few companies want to accept the risk of having an $80,000/year employee spend the summer babysitting a student intern. (The $80,000 yr/number comes from salary + benefits).

I'm on advisory committees for some high school biotech programs, and I've had student interns, so I know these students have an excellent track record and can be a great help. But, I also know how people in companies think. Hiring interns presents a risk for employers in terms of lost time and productivity.

Learning skills

Not only are internships important for investigating future careers, sometimes internship experience is essential for getting a job.

We still have the same catch 22 that I experienced in college. Biotech companies and University research labs want to hire experienced people, but they're unwilling or unable to provide that experience. Students need experience to get jobs, but they can't get jobs without experience.

Community college biotech programs have helped and Bio-Link centers have been instrumental in helping schools connect with companies. By focusing on marketable lab skills, those programs have become fairly successful at getting students into the workforce.

Many community college programs also require their students to do an internship.

But guess what, unless you have experience, those internships are still hard to get.

What can we do?

Stay tuned. We discuss different models in part II.

Subject: Education

technorati tags: biotechnology,
teaching-carnival
education
science education

Tangled Bank #51: the Seattle Tour!

2006-04-11T21:31:00.000-07:00

I've been racking my brain about what to do when Tangled Bank #51 came to Seattle.

And it hit me.

What do I normally do with visiting nobility (like my in-laws or my parents)?

We go sightseeing.

So come along, get your reading glasses and your walking shoes, we've got places to go and lots of scientific treats to sample along the way.

We're going to do a circle around the center of the city, starting in a bus ride to the zoo and ending up at our local cultural hotspot, Archie McPhee's.

Since I'm a biologist, we'll start our tour at Woodland Park Zoo. Before we're allowed in, we have to answer this riddle.

"Who's bald head makes it easier to dive head first into dead meat?" I think we'll let 10,000 birds answer that question and explain to us why Black is Back.

No visit to the zoo would be complete without a trip to the Tropical Rain Forest display. If we can be quiet, we might even learn from our docent, GrrlScientist, about the new species of parrot and mouse that were recently described from the small Philippine Island of Camiguin. Her enchanting display, New Parrot and Mouse Species Discovered in Phillipines, includes lovely photos and maps. It's right around the corner at Living the Scientific Life (Scientist, Interrupted). Woodland Park has lovely landscaping as well. Could they have saved some $$ if they bought their plants on eBay? Check out It came from eBay from the Invasive Species Weblog to learn some surprising facts about those bargain basement plants.

The petting zoo is always a popular stop. But be sure to wash your hands when you're finished. Tara Smith, of Aetiology, has an entire series on Emerging Disease and Zoonoses that explains why this is a good idea.

After we leave the zoo, we'll take a short stroll through Woodland Park and do some rabbit watching. The city plans to round-up most of the rabbits, sterilize them, and send them off to retire at a bunny farm (after Easter?) but I think the city should consider another solution. After reading Another Bobcat Story from the Dharma Bums, I wonder if we shouldn't look into getting a Mayan Jaguar carving and let Nature take its course.

Our next stop will be the Burke Museum of Natural History, but on the way we'll hike through Wallingford and check out one of my favorite landmarks, the Word of the Week. This week we'll fortunate to have two new words. From Bora Zivkovic at Cicadiana, we have a word to describe that feeling when in you've been in one place too long, Ah, Zugunruhe!, and from Wandering Visitor we have a photograph that might have been the model for "The Scream" and we have Pandiculation, a word guaranteed to make you very, very, sleepy.

Before we get to the Burke, we'll also make a quick trip inside the University Book Store to check out a new book that we read about at Living the Scientific Life on Darwin: Discovering the Tree of Life.

The Burke has lots of bones and interesting displays. We might even see some displays getting set up or moved around like the you can see in the Ice Age Migration web cam that Zygote Games shared.

Naturally, there are wonderful diplays on evolution. Science and sensibility wants to know why there's so much hoopla over a funny-looking fish. He invites you to read about the real winners of the first land race in When animals first conquered the land.

What's that PZ? You found some interesting fossils, too? Wow! Those are incredible. Take a look at the Taphonomy of fossilized embryos for some wonderful photos and interesting experiments.

As we leave the Burke, we'll walk through the University of Washington campus and pass by the old nuclear reactor. I wonder if there any Deinnococcus living close by. These radiation-resistant bacteria have been found living on the Hanford Nuclear Site in eastern Washington and seem to be ready for any type of environmental insult. But Hanford's too far away for us to visit today. We'll have to be content with reading Karmen Lee Franklin's wonderful story and looking at electron micrographs at Chaotic Utopia's Conan the Bacterium: The Ancient Microscopic Hero.

It's time now, to stop at the UW Health Sciences complex. Construction never stops in this part of campus. We can ask the Seattle SNP group about the study on aging that Jeremy Cherfas described in Why Die? at Another Blasted Weblog. A single nucleotide change in the APOC3 gene is correlated with a longer lifespan.

Glyn Moody writes about other interesting studies in genomics in Coughing Genomic Ink. I was fortunate to hear the subject of this piece, David Haussler, give a wonderful seminar at the UW and Moody does a fine job describing Haussler's work to reconstruct ancestral genomes.

Before we go on, and as long as we're talking about seminars, I have to add a story from Uncertain Principles on writing letters to famous figures in science (Origin Story). He would have been very impressed the night that Jack Horner talked at the UW. Kids were lined up in the aisles waiting for autographs!!!

We might also drop by the teaching labs in the biology department and ask if they have anything informative to say about The Three Types of Experiments that are described at The Daily Transcript.

No discussion about genomics is complete without considering the ethical implications of this line of work. I wrote about how these discussions differ a bit between classrooms and companies. Kate Were tackles a harder problem in a three part series (I, II, and III) on sperm donors and sexuality. Since Google has opened an office in the region, Hsien Hsien Lei at Genetics and Health wants us to ponder this idea: Google: A Threat to Genetic Privacy? What if Google were to become a gigantic version of BLAST?

Our next stop will be biotech companies and institutes near Lake Union. First, let's go to the Fred Hutchinson Cancer Research Center. I'm sure the researchers there would enjoy Charles Daney's article, from Science and Reason, Cancer Genes Tender Their Secrets. And they would certainly agree with Orac, from Respectful Insolence on Linus Pauling and clinical studies of vitamin C. (By Seed prodded, or there's less to these studies than meets the eye). I have to share a funny Linus Pauling story that was told to me by a former boss. He said that he once asked Linus Pauling how he detemined the appropriate dose of vitamin C to take. He (my boss) claimed that Linus said that he upped the dose until he got diarrhea and then backed off.

Let's go on. Close by the Hutch is the Seattle Biomedical Research Institute. Perhaps we can see some trypanosomes if their outreach scientists are on duty. I have a soft spot for Tryps since I studied them as a post-doc at the aforementioned Fred Hutch. Orac tells us Tryps are also a wonderful model that illustrates how evolutionary understanding furthers our understanding of biology, overall. (Medicine and evolution, Part 3: A trypanosome shows the way). It's a great article with wonderful pictures.

Time for a lunch break. Lab Cat has an enjoyable read, What is Food Science?, that's a perfect lunch time treat. Who would have guessed that there is a Research Chefs Association? or a trademarked field, with a somewhat erotic sounding name called Culinology®?

What better place to head after lunch than down south to the Museum of Flight? If the Museum of Flight had animal exhibits, I would suggest that they include these. From the Hairy Museum of Natural History, we have Sharov's Wondrous Wing. In the art section we could include the interesting paintings from Rigor Vitae and the story: Gliders and the evolution of flight. And we can't forget the incredible Gliding Ants from Science and Politics.

Time to head back north again. On to the Seattle Aquarium where we can see people embrace their inner fish. And the Pike Place Market where we can see the fish get embraced and then tossed around. I would like to see the guys at the Market toss Tiktaalik, the fish that Hitched to Everything writes about in We hit the jackpot. But I shudder to think what would happen if they only tossed the fish halfway there, as Whirled View explains in Tiktaalik and Zeno. If the fish paid more attention, maybe they could crawl on over to the tourists, we could spend our time musing about more general issues in tetrapod evolution like IndianCowboy (New Transitional Fish/Tetrapod Fossil And Other Thoughts).

Only two more stops left. No trip to Seattle would be complete without a visit the Specific appliance center, no wait, the magnificent defiance penter, oh right, the Pacific Science Center! And my home base, Geospiza is only two blocks away.

Pacific Science Center has one of the most wonderful collections of physics toys in the entire city. I think Scientia est Potentia would enjoy this place and it would be perfect for looking at Physics, Sex, and People in a Box-shaped Room. Well, maybe not the sex, actually. There are quite a few kids running around. But if any creatures behave just like random particles, it's a group of kids at the science center.

I think Stein from Dynamics of Cats would enjoy it too. Although it's pretty unlikely that the PSC could help fund the Terrrestrial Planet Finder, they're badly in need of funding themselves. If there is anywhere in Seattle where people might really enjoy Mark Chu-Carroll's discussions on Dimensions from Good Math, Bad Math, it would be at the PSC.

Now, we have to wait for the bus to Ballard and our last stop. Time goes so fast when we're having fun. Bora wonders if time moves faster at night because you're cold or because you're hungry? He'd like to have a group of undergraduates test this out (Chossat's Effect in humans and other animals), so if you teach a class, and want to do some relatively harmless human experimentation, let him know.

If you're worried that we won't see the bus coming, check out Cognitive Daily, where we learn about Seeing and awareness, or how fear can bypass the visual system.

At last, the bus comes to take us to Ballard. Ballard is the Scandanavian enclave of Seattle. This part of the city boasts the largest Syttende Mai parade outside of Norway. We better not let Ballard know about the discovery of the ancient Swedes between the ice (thanks Salto Sobrius for this story on the First People!) or we'll be finding settlements of Neanderthal Swedes down on Market Street for sure. You betcha!

Since we're in Ballard, and it's the end of the trip, we have to visit Archie McPhee's. After all, it's a cultural highlight of the city. Not only does Archie's have useful items like bacon strip bandages and the every popular Einstein and Librarian action figures, Archie's would be the type of place that would carry Professor Quippy's invention - the Cliffy Siren (from Mark Rayner). And if Archie's had pets, you could probably get an interview with a nude mouse, just as described in the Science Creative Quarterly.

Luckily, they don't sell chemicals like Bis(Chloroethyl) NitrosoUrea, otherwise known as:

BCNU.

Because our tour is over, and it is time for me to be BCNU.

If you speak English, be sure to say it out loud

and I'll BCNU, too!

Subject: Announcements

technorati tags: Tangled Bank, science

Ethical issues in biotechnology: contrasting companies and classrooms

2006-04-06T16:56:00.000-07:00

About a decade ago, I took a fascinating summer course at the UW on bioethics. We read about the Nuremburg trials and the Geneva conventions. We learned about horizon problems and eugenics. And we discussed lots of challenging scenarios with genetic testing, autonomy, family relationships, and the problems faced by people seeking to have children, trying to get insurance, or looking for a job.

So naturally, when I started a biotechnology course for non-science majors (Biotechnology and Society) at our community college, I used many of those examples. The class had a grand time discussing all those interesting things. And they all had opinions! We debated the merits of labeling GMO food, animal testing, genetic tests and all sorts of fun topics. We had a great time during the OJ trial, studying good and bad DNA fingerprinting data and the chain of custody. And considering all the vegetarians in our class, our talks on making cheese were especially enjoyable. Since many of our vegan students were also anti-GMO, it was truly enlightening for them learn about the GMO E. coli used to make rennin for vegetarian cheese.

Later, when I became a member of Bio-Link in 1997, one of our goals was to address teaching ethical issues related to the biotech industry.

I decided it was time to find out what they were so, I asked members of our industrial advisory board.

What are the most important ethical issues in your company?

These were the sorts of answers I received:

Make sure your students know that they need to write down every thing in their notebooks! Even – no, especially if it didn't work. I fire people for not recording negative results!

They need to take good notes and understand what they're doing. I had to testify in court, in a patent dispute, about experiments that I did many years ago as a technician.

They need to know that telling the truth is critical!

They need to know that we work with animals, people have taken shots at our building, and sometimes I've had to walk around protestors to get to work. If they have problems with animal research they should do something else.

Make sure they know that experiments cost money!

I listened and modified my seminar course for biotech majors to better align with industry concerns. We had speakers talk about patent disputes, interpreting data, and animal research. We had speakers from the FDA talk about their role in making sure that biotech products are safe (although, I guess you want to stay away from diet pop).

Perhaps our biotech program was a bit unusual, though, because from what I read, biotech instructors spend more time on interesting controversial topics and miss the topics that concern biotech companies.

This gap can be seen very clearly when comparing what teachers say they teach (genetic testing, euthanasia, cloning, stem cell research, GMO foods) with the top ethical topics concerning companies. According to Finegold and Moser (1), in the March issue of Nature Biotechnology, the top ethical concerns of companies were these:

Employee behavior
Conduct of clinical trials
Sales practices
How to market products
Corporate governance
Regulatory strategy
Who to partner with
What research to conduct
What products to develop
Accounting practices
Company mission
Where to do business
Product pricing

We don't do clinical trials, but I'd say this list is pretty much correct, given my limited company experience.

Which raises an interesting point.

Could it be that biotech instructors are biased towards picking more interesting topics? Few things could be worse than lecturing on accounting issues to biotech students.

Or perhaps this list is different from the standard garden-variety set of classroom biotech issues because some of the ethical stands that people might take should discourage them from working in companies that engage in those activities in the first place.

Against animal testing? Forget working in a biotech company. Almost all of them rely on animal tests somewhere down the road.

Against GMOs? That rules out any agbiotech companies, plus several other biotech companies that might be doing research to express therapeutic proteins in tobacco or corn.

Have a problem with stem cells? Many biotech companies that make or do research on developing therapeutic drugs are interested in this technology. If they're not doing this work in the U.S. they might be outsourcing this work to countries with a more enlightened view.

Against cloning? The whole industry, just about, is based on cloning something - either DNA, cells, or bigger things.

Euthanasia? Dead issue. (oh sorry! I just couldn't help it!) Rest in peace, we're not planning a product line around this one.

Hmmm, on second thought, maybe the classroom topics are on target after all. Could the answer be that biotech instructors want to help individuals avoid a rude shock by thinking about where they want to work and why, before they apply for a job?

1. David Finegold & Allison Mose. 2006. Ethical decision-making in bioscience firms. Nature Biotechnology 24:285 - 290.

Subject: Education

technorati tags: biotechnology,
teaching-carnival
education

Tangled Bank is coming April 12th!

2006-04-04T09:18:00.000-07:00

Hey there aspiring science writers!

Warm up your typing fingers and get to work 'cause the very famous Tangled Bank will be hosted here on April 12th.

Your assignment is to send essays, reviews, and interesting things for me to post and the rest of the world to chew on and puzzle about.

Weird science entries are especially welcome. : P

Send your submissions to: sandy at geospiza.com

or to: host at tangledbank.net

If you'd like to see past issues of Tangled Bank, simply click the image below to go check out the archives:

Subject: Announcements

technorati tags: Tangled Bank, science

Happy Sun-Earth Day!

2006-03-29T07:51:00.000-08:00

photo from NASA's image gallery.

I guess there was a live webcast from Turkey this morning (2:00 am PST) of a total solar eclipse. Needless to say, I missed it due an earlier appointment with my pillow.

But it doesn't matter. You can satisfy any urge to see an eclipse over the web at NASA's video gallery. There are 5 short videos of past eclipses that are lots of fun and even one of my favorite technologies, podcasts! I haven't listened to any yet, hopefully they'll be as good as the Stardate radio shows on NPR.

The video gallery includes animations that describe what's happening during an eclipse. Personally, I still like the old fashioned method for teaching these ideas. Outside of seeing an eclipse in person or watching the eclipse videos, nothing beats making an eclipse with a flashlight and a couple of oranges.

Subject: Web resources

technorati tags: astronomy, eclipse

Sugar, Sugar ...

2006-03-24T17:40:00.000-08:00

As of March 24th, over 186 people have tested positive for the avian flu virus (H5N1) and 105 are dead (1).

This is a nasty kind of flu.

Luckily, most of the cases, so far, have been in our avian friends and their human companions. Health professionals all over the world, though, are warily watching web sites and looking for signs that people are catching flu from other people. Everyone wants to know the point when it's no longer strictly for the birds.

But for the moment, we're okay, it seems like the avian flu doesn't spread easily from one human to another.

And now we know why.

Two reports this week, in Nature from Shinya, et. al.(2), and in Science from van Niel, et. al.(3) provide the answer.

Avian flu, it seems, likes to stick to a certain kind of sugar. That modified sugar, is a sialic acid with an alpha 2,3 link to galactose, and is joined through other sugar residues to the surface of special kinds of cells. At one time, flu researchers didn't think humans had these specific kinds of cell-surface sugars. But both of research groups found extra-special sugar coating on the surface of cells, deep in the lungs, and confirmed that these were the cells that got infected.

Van Reil and colleagues found this result by mixing inactivated viral particles with tissue samples. They used fluorescent antibodies to see where the virus stuck and which kinds of cells it liked.

Shinya, et. al. stained infected tissues with lectins to see what kinds of sugars could be found on different cells. They also stained infected tissues (epithelial and alveolar) to look for viral particles.

Since the cells that get infected are located deep in the lungs, any new viral particles produced through an infection have to travel a long distance in order to get out of the mouth and infect someone new. This would make it harder for the virus to infect a new human because it doesn't escape the body through a simple cough or casual sneeze.

How is this different from the current human flu?

The influenza strains that are doing most of the damage, in humans this year, bind to a different kind of sugar than the avian strain. The human flu sticks to a sugar with an alpha 2,6 link to galactose; unfortunately for us, this sugar is found on cells in the nose and upper respiratory tract. This makes the human flu more infectious (for us) since it can travel long distances with a good strong sneeze.

Click the drawing to make it bigger. But be warned, I took some liberties here. Influenza is usually drawn like it comes from outer space. Typical images show lots of spikes to represent the hemagglutinin and neuraminidase molecules on the surface of the particle. Also - the cell and the virus are not drawn to scale.

What does this mean? Are we safe?

No one knows. Some experiments earlier this month, by Stevens, et. al.(4) found that it only took two mutations, in the right positions, to change the specificity of a hemagglutinin from one kind of sugar to another. No one knows how many mutations would be needed to change the specificity of the H5 hemagglutinin. Neither do we know much about the probability that this will happen (although I'm sure this is something that could and should be examined by mathematical modeling).

It could happen.

References:

1. World Health Organization. WHO Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. (www.who.int). (accessed March 24, 2006).

2. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. 2006. Avian flu: influenza virus receptors in the human airway. Nature. Mar 23;440(7083):435-6.

3. van Riel, D., Munster, V., de Wit, E., Rimmelzwaan, G., Fouchier, R., Osterhaus, E., and T. Kuiken. 2006. H5N1 Virus Attachment to Lower Respiratory Tract. Sciencexpress. www.sciencexpress.org

4. Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA. 2006. Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus. Science. Mar 20; [Epub ahead of print]

Subject: Microbes

technorati tags: virus, avian influenza, bird flu, influenza

Look at the wee animalcules!

2006-03-23T06:58:00.000-08:00

A new Animalcules has been posted. This week's issue contains stories on Plasmodium, papilloma virus, antibiotics, influenza, and other interesting bits.

Stop by and take a look. And, consider submitting a story to one of the next issues. It's a low pressure way to share subjects that you enjoy.

Read away and wash those hands!

Sequencing a Genome: the video

2006-03-21T09:58:00.000-08:00

Have you ever wondered how people actually go about sequencing a genome?

If they're sequencing a chicken genome, do they raise chickens in the lab and get DNA from the eggs? Does the DNA sequence come out in one piece? Why is there so much talk about computers? What are Phred, Phrap, and Consed? What is the Golden Path?

Wonder no more!

You too, can take a virtual tour of the Washington University Genome Center.

I found this really excellent series of short videos that follows two genetics students, Libby and Bryce, as they meet on the bus to the Genome Center and learn about all the steps involved in sequencing a genome.

A kindly tour guide takes Libby and Bryce through an amazing number of core labs, where they see gallons of media getting made. Among other things, they watch robots pick colonies of bacteria and inoculate broth. They see capillary tubes transport sequencing reactions into genetic analyzers and they see lots of people sitting in front of computers. All the steps are presented nicely and there a number of short animations to help visualize concepts such as growing E. coli that contain BACS (Bacterial Artificial Chromosomes), restriction mapping, and PCR.

Not only are these videos helpful for students who want to learn about biotechnology, these videos are helpful for bioinformatics groups and software companies like ours. Although some of us grew up sequencing DNA, a large fraction of the programmers and software engineers at Geospiza, did not. We routinely send our development team on field trips to a local genome center so they can learn what technicians do. Now, we can refer developers to the genome video to see where the samples go and learn how people work with all those robots.

I like this video, too, because it shows scientific careers that do not require a Ph.D. All too often, people think the only jobs in science involve heading up a laboratory, and they forget that industrial-scale science requires many different kinds of abilities and offers several different opportunities. In fact, a large number of the people working in facilities like genome centers have bachelor's degrees or 2-year degrees from community college biotechnology programs.

Even if you've done some sequencing yourself, it's still interesting to see how the Wash. U. genome center has turned DNA sequencing into an industrial scale process.

I, for one, never knew that so many genome technicians wore baseball caps at work.

Subject: Web resources

technorati tags: biotechnology, genomics, DNA sequencing

When Mt. St. Helens moves her bowels ...

2006-03-16T09:04:00.000-08:00

brown water flows out of faucets in Arkansas.

A simple little earthquake on March 7th, 2006, and 22 hours later, there were calls about brown water in the Feliciana Parish.

“People don’t want to believe me when I say an earthquake caused their brown water, but it’s true,” John Hashagen said.

Hashagen said he began looking into the possible effects of seismic waves on the Laurel Hill wells after reading an article in WaterWorld, a magazine for the municipal water industry, on the effects the March 1964 Alaskan earthquake had on water systems across the country.

Not only did the utilities chief uncover a possible connection between west coast earthquakes and discolored water, he found a way to use that information.

Apparently there are only two wells in the area that are sensitive to seismic activity.

Hashagen said he and water district employees can prevent the wells from pumping the discolored water if they learn about an earthquake hundreds or thousands of miles away in time to temporarily shut down the wells.

So, he signed up for earthquake alerts, via e-mail, from the U.S. Geological Survey. Whenever a quake occurs that measures over 5.0 on the Richter scale, he gets the message and shuts down the wells.

The brown water happened on March 8th because the March 7th earthquake was too small to trigger the e-mail alert (only 3.1 on the Richter scale).

I think if Dave Barry were a science teacher, this is the kind of stuff he would love.

Thanks are due to the WSTA for sharing the fun!

Subject: Weird Science

technorati tags: geology, earthquake

3/39/2006 Update: It should be noted that the geological jury is not convinced that Mr. Hashagen is correct. He might be right, Mt. St. Helen's movements might truly be connected with the funny colored water, but a bit more science needs to be done before geologists will believe that the connection is real.

How would you test this? What sorts of data do you think need to be collected and analyzed in order to test Mr. Hashagen's hypothesis?

Doing the cross-species hop

2006-03-15T09:42:00.000-08:00

What allows a virus to begin infecting a new species?

This question concerns many people these days as we anxiously watch the skies. When will avian influenza obtain the capacity for human to human transmission?

It seems in the case in parvovirus, that a rapid mutation rate may be a key. If a virus can quickly mutate, some of the progeny might be better adapted to the new host.

HHMI news has a nice description of a fascinating study, recently published in the Journal of Virology, that extends work published last year in PNAS (1).

The authors look at the evolutionary changes that occured when the feline panleukopenia virus made the switch and began infecting dogs. Once the virus began to infect dogs, mutations began to appear more rapidly, paving the way for dog to dog transmission. It's an amazing and nicely done piece of work that helps illustrate why evolutionary studies are important.

Or perhaps it's just a case of the cats getting their revenge.

References:
1. L. Shackelton, C. Parrish, U. Truyen, and E. Holmes. 2005. High rate of viral evolution associated with the emergence of carnivore parovirus. Proc. Natl. Acad. Sci. 102:379-384.

Subject: Microbes

technorati tags: virus, microbiology

When will students do science with computers?

2006-03-14T19:28:00.000-08:00

Two puzzling streams of thought have merged lately, leaving me in an eddy of confusion.

In the first stream, swim my observations of the kids in our house. We bought computers for both of our kids with the naive parental notion that they would be important for school.

I still think they are important. And both kids do use their computers routinely.

But, do they use them for school?

Not much. Computers, it seems, are all-purpose entertainment centers for watching DVDs, working with digital photography, communicating with friends through instant messaging, Skype and e-mail; and for organizing music.

None of their classes have the kids use their computers, with the exception of language arts or history classes where they mostly use them for writing papers.

As a scientist, parent, occasional community college instructor, and someone who writes instructional materials for science students, I'm mystified by this observation. Why don't our kids use computers for subjects like science and math? They could be making cool graphs and doing statistics or writing algorithms with programs like Excel. Their science classes could have them looking at GIS data, working with Google maps, searching DNA sequences, or doing fun things with molecular modeling.

I felt like a subversive when I showed my oldest daughter how to use the NCBI Taxonomy database to identify kingdoms and phyla. There are so many wonderful resources out there and I know some high school and community college teachers do use them, but I also know my kids do not.

Why don't our kids use computers for science and math?

The answer to that question lies floating in the second stream but it's a tricky one to catch hold of.

Is it lack of training?

Is it lack of money? Are the school districts short on computers?

All of these are at least partly true.

This report and quote from the National Science Foundation certainly implies that lack of computing experience could be a factor.

America's Pressing Challenge - Building a Stronger Foundation, Feb 23, 2006

Technology has its separate challenges. Teachers must shift from being "familiar with" computers to being able to more effectively use computers in support of their instruction. Most of their students are already entering school computer literate, but "do not have a grasp of the science and engineering that underlie that technology."

Lack of money could be another factor. Many science teachers share a computer lab with several other classes, so getting the lab requires a combination of advance-planning and finely-tuned negotiation skills. Still, many teachers will do an activity or two in the computer lab, and never assign outside computer work except for writing papers.

But when I ask teachers, "Why don't high school or community college students learn how to use the computer as a scientific tool?"

I get a different answer.

The teachers, I know, say they won't use computers for science assignments because there are students who don't have home computers.

Admittedly, my sample size is small and non-random, but I've heard the same answer, verbatim, in different parts of the country.

I understand being reluctant to add assignments that require computers that students don't have. But aren't there any other options? I find it strange that this reluctance (as far as I know) only appears in the science and math classes. Language arts teachers require typed papers. Do they ask if kids have computers first? Are science students the only kids in the world still using typewriters?

Universities and private high schools don't seem to have this problem. They just require all students to get computers.

The report above indicates that the NSF believes it's important for kids to learn how do science with computers. Five years ago, in 2001, 70% of the households in Seattle had on-line access, causing it to rank 2nd in the nation in terms of wired cities. Given the large fraction of households in Seattle that have computers, and the number of parents who say they buy them for their children, it seems like parents want their kids to become adept with technology.

But how will kids acquire these skills? If their teachers won't assign the technology, the kids will have to work to learn it on their own, and somehow manage not to be distracted by all the entertainment opportunities that computers offer instead.

Personally, I don't think many public school students will be able to teach themselves how to use computers for scientific research. At least, not until they have guidance from their teachers and access to computers beyond the occasional day in the computer lab.

So right now, judging from what the teachers say, the only kids who will learn computer skills in school will be the kids whose parents can come up the 20K per year for private school tuition.

What is the best answer to this puzzle?

The ideal situation is one where every student has a computer. But how do we get there?

Perhaps high schools, and maybe community colleges, could start loan programs, like they do with graphing calculators. True, laptops are more expensive, and more difficult to maintain, but I think, given the choice between no computer assignments and helping out with a loaner program, parents would help out. It's far cheaper for parents to buy a computer and help chip in for additional loaner computers than to pay $80K for four years of private school.

If all kids had computer access, science teachers might give computer assignments and all our kids might have a chance to learn how to use computers for doing science.

Until that day, it seems that public school science classes just won't compute.

Subject: Education

technorati tags: bioinformatics, education, science
science education

Hunting for huntingtin V: BLASTing on forward

2006-03-13T20:17:00.000-08:00

This is the fifth article in our series on using digital biology to investigate Huntington's disease. Right now, since we know that extra glutamines are linked to Huntington's disease, we would like to know if other genetic diseases can result from extra glutamines.

If you wish to learn more about the story, the previous articles are described below. Or you can jump ahead and go straight to today's episode.

Hunting for huntingtin, part I Background, reviews, biochemistry of glutamine, and a bit of comparative genomics

We were quite busy in part I. We learned about Woody Guthrie, found an interview with Dr. Nancy Wexler, and got a bit of background information on the huntingtin gene.

We used the UCSC genome browser to see if other creatures have the huntingtin gene and a similar gene structure.

We asked if the extra glutamines caused the disease and looked at experiments where the Jackson Labs tested this idea in mice.

Last we looked at the structure of glutamine and mused about why lots of glutamines might cause problems for a cell.

Hunting for huntingtin, part II In which we're reminded that database searches are experiments, too.

We discover that the polyglutamine regions are missing from structures with polyglutamine and we are unable to find polyglutamine sequences in GenBank

Hunting for huntingtin, part III Our continuing search for proteins with polyglutamine

In which we learn what happens to low complexity sequences in a blastp search.

Hunting for huntingtin, part IV: What did you expect to find?

In which we learn how to adjust the blastp parameters so that we can find proteins with polyglutamines

************************************************************

Enough of the recap, on with the experiment!

It took a few trys to figure out how to do the experiment. Now that we know how to do it, what should we do first?

We should learn a bit more about blastp. Nothing scary, mind you, but it's nice to have an idea how the information we put into a program is related to the output. So, before we go on, we're going to do a little experiment with blastp and see what happens when we search with different numbers of glutamines.

(We could also read about blastp, but hey, experimenting is more fun!)

Here is an image compiled from our colorful results:

I stopped at 50 since the scores didn't really change after that point.

Notice, how the length of our query sequence (lots of glutamines, abbreviated as Q) is related to color code. The color code, as shown in the color key above each alignment, is based on the alignment score. Scores in certain ranges are colored certain ways. You can see as the length of the match increases, the color changes, too. Our polyglutamine sequences give us a nice way to look at this relationship because we're using the same amino acid.

Why is that important? Keep reading and wonder no more!

I'll give you 10 points for a good match!

Did you ever think that calculating blastp alignment scores might be kind of like a game?

Indeed, it's a great game.

You get different amounts of points for matching different amino acids. And if your amino acids don't match, you get a penalty. The scoring table (also called a "matrix") is shown below. Click on the image to see it appear a bit larger, if you like.

I highlighted the value that's assigned when a glutamine (Q) matches another glutamine (Q). If one glutamine matches another, we get 5 points. Yeah!

Our final score is calculated by tallying up the points for each position in two aligned sequences. If we match 10 glutamines in a row, we get 50 points. We multiply by some mysterious factors (that may be discussed later) and finally, we end up with a score around 24.

Can I use my alignment points like frequent flyer miles? Who made the score sheet?
Why does matching another glutamine get 5 points and having a C (cysteine) match another cysteine get 9 points? Or when a W (tryptophan) matches another tryptophan, it gets 12 points?

Steve and Georgia Henikoff came up with these scores by looking at blocks of aligned sequences and determining how often a particular amino acid was replaced by a different amino acid (1). If the same amino acid was almost always found at the same position, it was assigned a higher score (i.e. W, tryptophan).

Notice, too, that our table has a row with a *. The * represents a position in a sequence where one amino acid is missing. Missing amino acids get assigned a negative score (-4) because they're are less common. This is probably because amino acid changes, in important regions, would harm the protein structure and impair the function.

We also get points if an amino acid is replaced by one with similar chemical properties. For example if we replace a lysine (K) with an arginine (R), we still get 2 points, because both amino acids have a positive charge. (If you want a key with chemical structures, or a key to the abbreviations, you can get them both here).

How do different numbers of glutamines affect the blastp results?

The graph below shows what happens when I do blastp searches with different numbers of glutamines. It only takes 10 glutamines to change the E value from 33 (not very significant) to 0.0001 (very significant).

The scores change a bit more slowly. I was surprised to see the relationship between the number of glutamines and the number of hits. Intuitively, it seemed to me that a smaller number of glutamines should match more things in the database. But the results contradict that notion.

Why did that happen?

When in doubt, look at the data

Looking at the sequence alignments shows why we see more hits. The results (below) show that when we we're using a repetitive sequence like QQQQQQ ... etc. and we use a longer query sequence, the query can start aligning to a database sequence at a greater number of points (and still have enough matching amino acids match to score as a hit). See how the alignment starts at 1, then 2, 3, and 4? This means that our query sequence can align to the same database sequence in multiple ways.

Longer query sequences can also tolerate gaps and more amino acid changes; yet still match enough amino acids to register as a hit.

So, in this case, a greater number of hits doesn't really mean that we're finding more sequences in the database. We're just finding the same sequence more times.

Do we only care about the number of hits?

No. Of course not. We do learn which proteins contain lots and lots of glutamines.

Stay tuned, next time we look at results.

References:
1. Henikoff, S. & Henikoff, J.G. (1992) "Amino acid substitution matrices from protein blocks." Proc. Natl. Acad. Sci. USA 89:10915-10919. (PubMed)

Subject: Doing biology with bioinformatics

technorati tags: biology, blast, , genetics, DNA

Birth of the Biotech Boosters

2006-03-10T09:09:00.000-08:00

Many years ago, long before my kids were high school age, I joined the steering committee of a brand-new biotech program that was starting at a local high school. A local company (Immunex) had pushed the Seattle school district to start the program and provided start-up funding. There was a brand new lab, additional money from another local company (Zymogenetics) and a strong feeling of energy and optimism for the future.

In the early days, funding was good. Immunex and Zymogenetics helped provide funding, and a grant from the Stewart Foundation gave teachers time for curriculum development and working on the program.

But corporate sponsorship can be a fickle thing. One of the major supporting companies, Immunex, was sold to Amgen and we all learned that Amgen was a different sort of company. Former Immunexers tried to maintain local outreach programs but many of the outreach activities were still lost. Former Immunex employees do continue to volunteer in the community, and Amgen still funds some community activities, but unfortunately, much of the support for high school programs has gone. Corporate sponsorship disappeared along with former student internships.

This left the biotech program in a quandry. Biotechnology is a laboratory science and science labs require consumable supplies, like enzymes and agarose and buffers. These aren't items that can be picked up at the local grocery store and they're expensive. If students are going to learn how to clone genes and work with DNA, they have to have equipment and supplies.

Our steering committee was composed of people with scientific backgrounds and little experience in fund-raising. Writing grants was a possibility but it's easier to get money to start something new than money to maintain a program.

About the same time, my oldest daughter started high school and I gained a new appreciation for the reality of funding anything at the high school level. In her first year, she joined both the soccer team and the biotech program. Instantly, we were bombarded with fees and funding requests. There were $50 activity fees for participating in sports, donation requests from the sports boosters starting at $150, yearbook fees, picture fees, all kinds of fees. Here a fee, there a fee, everywhere a new fee. Still, when you contrast these fees with the cost of $20,000 a year for a private school, public education at a good school is a great bargain. Our school district has serious money troubles, so none of the fee requests were really too surprising.

The surprise was the lab fee for the biotech program. The program asked for a lab fee of $8. As a parent, we had paid more than that for individual elementary school field trips. This was a shock! If I estimated that there were about 180 kids total in the program, the lab fees would bring in less than $1500. This wouldn't even cover the costs for a couple of field trips, much less allow the school to replace broken glassware, pay for supplies, fix broken pipettors (that cost $200 each), or purchase any new equipment. Our community college program had cost about $8000 per year for supplies and we had ten times fewer students than the number in the high school program. It was clear that the lab fees weren't going to be enough.

We realized it was time to learn from the sports boosters and make our own appeal to the biotech parents. We wrote a letter requesting their help and followed it with phone calls to all the parents. Not only were the parents supportive, they were surprised to learn that the biotech program needed funds and their help. In response the parents started the biotech booster group.

Since that time, the biotech boosters have helped out in many ways, including:

Donating funds
Finding mentors for students
Helping to find internships for students
Finding scientists and biotech professionals to judge student talks

The Biotech Booster help has been very worthwhile. We still can't take adequate funding for granted, but now, at least, there's a way to ask for help. A yahoo e-mail group keeps parents more informed about happenings at the school and gives teachers a more convenient way to transmit information. Communication between parents, steering committee members, and teachers has increased. Parents know more about the different milestones that occur in the program and can find out what their kids are going to encounter. Events like the Biotech Expo, the bioethics presentations for scientists, field trips to SBRI, mentor events, and applications for internships, are no longer mysterious things that happen under parental radar.

All too often, I think, parents become less and less involved once elementary school is over. Having a booster group has helped open a door and made it possible for parents to become more active in supporting their child's academic education. It gives parents a way to show that academics are valued at least as much as the extracurricular activities like football or band.

Subject: Education

technorati tags: biotech, education

A Birthday Celebration with Goofy Minnesota Limericks

2006-03-09T05:22:00.000-08:00

GrrlScientist invites you all to attend a surprise virtual birthday party for PZ Myers.

While I've never met PZ, I have enjoyed reading his blog, Pharyngula, and learning new things about embyros and the mysterious things that go on when cells divide and develop. Plus, PZ's brainchild, TangledBank is always a wonderful collection of fun things to read.

It's hard to know where the party is beginning or ending, but if you've ended up here, imagine yourself eating a piece of chocolate cake with pink amaretto frosting, while you can enjoy these goofy Minnesota limericks. Don't worry if they don't make any sense, I try to avoid sensible poetry.

There once was a young man from Morris
whose head was extreme-i-ly porous
his thoughts just leaked out
as he typed them about
and we're all waiting now to hear more o' this

Our fishing is fancy year round
the loon makes a strange erie sound
the canoe is a leaking
so when no one is peaking
napping is where we'll be found

You betcha by golly, it's fun
playing cribbage and waiting for sun
we've got cabin fever
in the lodge like the beaver
we'll come out when the winter is done

The snow is abundant in March
in August we all start to parch
we get eaten by mosquitoes
while we're chomping on fritos
Would it help if we all used more starch?

I once lived near Lake of the Isles
and skated around the goose piles
In my city of green
with the unearthly sheen
I rode my bike on the trails that went miles

In St. Paul every year there's a fair
whose size there is none that compare
we've heard some say "Texas?",
but most they say "not this!"
Minnesota's the place, that we'll share

Subject: Silly items

A day at the Biotech Expo

2006-03-07T09:11:00.000-08:00

Today, I'll be your tour guide on a journey through Biotech Expo. We'll begin our trip in creative writing with the exploration of complicated family ties and genetic entanglements.

Next, we'll look at some modeling activities. The gentlemen on the right used an ecology program with sheep, wolves, and bushes, to simulate what might be happening inside your nose. The sheep represented bacteria or viral particles, the wolves, our immune cells, and the bushes, were the nose cells. These students examined the impact of changing the number of immune cells or the numbers of bacteria on the overall health of the nose.

Another modeling project is shown on the left. This model was made by cutting out shapes from some kind of squishy material and sticking wires through them. Very colorful!

On the right is one of our high school researchers describing her project to some of the judges. A winner in two categories, her project compared methods for isolating DNA for genotyping and the reproducibility of the different methods. She put her AP statistics class to good use!

"And when you smile for the camera..."

Serious drama students are always up for an interview with reporters, especially when they bring a film crew.

Today's tour will have to bypass the popular musical performances, and exceptional projects on journalism, multimedia, teaching, website design, and histology since a day at the Expo passes by quick and our tour is running out of time. Fortunately, we will not miss out on biotech art. Below, on the right we see a beautiful painting of yellow Trypanosoma gambiense swimming around in a pool of red blood cells. On the left, we see a drawing with both the science and consequences of multiple sclerosis.

The yellow busses are lined up and ready to depart. If you listen closely you can hear hands clapping from thousands of parents, thanking the dedicated organizers at the Northwest Association of Biomedical Research, and all researchers and biotech people who volunteered to be mentors or judges.

The tour is over

. . . until next year.

Subject: Education

technorati tags: biotech, education
science education

What's that stuff?

2006-03-04T10:24:00.000-08:00

Have you ever wondered about Cheeze Whiz? why new cars have a distinctive smell? or what makes golf balls so springy?

Chemical and Engineering News, published by the American Chemical Society, has a wonderful section that you will certainly appreciate.

"What's that stuff" is a collection of entertaining stories about the stuff we encounter in everyday life. Each article combines chemistry with history and fun facts in a way that entices the reader to stay awhile and read every one.

Since the stories are written for non-chemists, they make a perfect companion to chemistry courses ranging from high school and beyond.

Many of the articles would be great in non-chemistry courses, too. For example, the articles on chocolate, Jell-O, ice cream, margarine, MSG, licorice, and chili peppers would be great assignments for any nutrition or cooking class. Microbiology students would enjoy reading about food preservatives and pasteurized foods. Environmental science students could read about bug sprays, plastic bags, cement, asphalt, and artificial snow.

Even artists, cosmetology, and fashion students would find something here to spark their imagination. Stories on sunscreen, ink, fireworks, hair coloring, self-tanners, and lipstick are sure to appeal.

With articles on topics that range from Silly Putty to Lycra, and catnip to champagne, this site is sure to answer some questions along with raising a few new ones.

What is kitty litter anyway? Now, I'm going to have to find out.

Subject: Chemistry

technorati tags: teaching-carnival, chemistry

Build your own virus

2006-03-01T10:15:00.000-08:00

Build your own virus! is a simple, quick, and fun game that provides a good way to introduce students to features that are used to distinguish viruses.

The game works like this:

First, you choose whether the virus has an envelope or not.
Next, you choose whether the genome is single or double-stranded.
Then you pick your favorite kind of nucleic acid - RNA or DNA
Last, you decide if the viral particle should be small, medium, or large.
And the site tells you what kind of virus you built (computer is not a choice!).

A good memory game is to pick a virus and try to remember it's characteristics to see if you can get it built.

Subject: Web resources, Microbes

technorati tags: virus, microbiology

"I hear the cottonwoods whispering above.."

2006-02-27T19:58:00.000-08:00

Some people say that science takes the magic out of everyday life.

Not me!

I've learned some things by reading Science (1) that might give nightmares to some people, especially young children.

Remember that scene in "The Wizard of Oz" when the trees start hurling apples at poor Dorothy?

Now we're learning that the trees would really defend themselves by giving poor Dorothy a tummy ache.

Pardon me a moment while I apologize to enforcers of precise scientific language.

Okay, okay, the trees probably have an evolutionary benefit if Dorothy eats the apples and kindly deposits the seeds in a nice rich pile of human fertilizer after her body is done with them. The trees would really only fight back if Dorothy chomped a bit on the leaves and bark.

Nevermind, this is even better. The trees talk to each other.

How?

We learned last week that plants move more than you think, but it's not that. Even if a tree waved its branches frantically around, the other trees wouldn't see it. After all, they don't have any eyes. (Well, someone had to say it.)

But trees have other abilities that we don't see.

Trees (and other plants) can communicate by passing gas. You may not have gotten the point, but you've probably received some of the messages.

For example, if you walk around on the Berkeley, CA, campus, you know there are Eucalyptus trees around. You can't escape the smell. (The first time I visited, I thought someone must really be into cough-drops.)

Eucalyptus trees make over 30 volatile compounds (2) that contribute to that unusual smell. At least some of those compounds are messages to other trees. And a pine forest, what is it saying?

This first time I heard this fanciful idea of trees talking to each other was when I was in graduate school. This was back in the days when we had to walk five miles in the snow to get the lab (Oops, wrong story!).

One of the students and a post-doc in our lab made subtractive cDNA libraries to try and find wound-inducible genes. They were hoping to find some of the genes for making those tree-talking molecules, but their tools were a bit too crude.

Now, in the Feb. 10th issue of Science, there are some great articles that describe more recent experiments showing that the talking tree hypothesis is correct, at least for a few plants.

Baldwin et. al. describes some wonderful experiments where researchers observed that tobacco plants get eaten less when they live near sagebrush. Using microarray technology and sensitive analytical instruments, they found that the sagebrush produced all kinds of volatile compounds that traveled through the air. They also found that nearby tobacco plants responded by turning on new genes.

When tobacco plants heed the warning, they make a proteinase inhibitor. Since the proteinase inhibitor makes it harder to digest protein, the leaf-eating animals probably feel a bit ill after chewing those tobacco plants. Maybe they swear off chewing tobacco for good! Or maybe they decide that next time, they'll try a different brand.

Whatever goes through the murky minds of the herbivores:

When sagebrush talks, tobacco listens.

References:

1. Baldwin IT, Halitschke R, Paschold A, von Dahl CC, Preston CA. Volatile Signaling in Plant-Plant Interactions: "Talking Trees in the Genomics Era." 2006. Science. 311:812-5.

2. Zini CA, Zanin KD, Christensen E, Caramao EB, Pawliszyn J. Solid-phase microextraction of volatile compounds from the chopped leaves of three species of Eucalyptus. 2003. J Agric Food Chem. 51:2679-86.

Subject: Plants

technorati tags: biology, nature, plants, trees

I want my plant TV!

2006-02-24T12:17:00.000-08:00

A long time ago, I saw a Star Trek episode where the crew encountered aliens who lived at a different frequency. I may have this backwards, but I think the aliens moved so quickly that no one knew they were there. And until problems struck, our heroes were happily oblivious to the existence of the others.

The Plants In Motion movies remind me of that episode. Since plant movement occurs much more slowly than movements we can easily observe, we tend to think that plants don't move. These movies prove that idea wrong. Filmed with time-lapse photography, these short movies show seeds germinating, beans dancing to circadian rhythms, twirling vines, flowers bursting out with passion, and many other activities that we simply don't see because they happen at a different rate.

I think a collection of these movies on a DVD, with a good soundtrack, could be a lot of fun. It wouldn't have quite the impact of Jumanji or Invasion of the Body Snatchers, but it still might inspire a deeper appreciation for the plants in our lives.

As for the background music, my vote goes to: "Feed me, Seymore!"

Subject: Web resources, Plants, Silly

technorati tags: biology, nature, plants

Digital Biology course info is posted

2006-02-23T16:37:00.000-08:00

A few months ago, I posted a note about the two courses that I will be teaching this summer in Austin, together with Dr. Linnea Fletcher (Austin Community College).

The information is now on-line, so you can ahead and register. The courses and dates are:

A Hands-On Tour Through the World of Bioinformatics
LINEA FLETCHER, Austin Community College and SANDRA G. PORTER, Geospiza, Inc.
June 8-10, 2006 in Austin, TX

Studying Evolution with Bioinformatics
LINNEA FLETCHER, Austin Community College SANDRA G. PORTER, Geospiza, Inc.
June 12-14, 2006 in Austin, TX

If you have a topic request, let me know. I've been working on some things with influenza virus, HIV, genome browsing, mutant structures, and green fluorescent protein. So we should have lots of fun.

Subject: Announcements

Sequencing the campus at the Johns Hopkins University

2006-02-17T13:59:00.000-08:00

A few years ago, the General Biology students at the Johns Hopkins University began to interrogate the unseen world. During this semester-long project, they study the ecosystems of the Homewood campus, and engage in novel research by exploring the microbial ecosystems in different sections of the campus. Biology lab students gather environmental samples from different campus ecosystems, isolate DNA, amplify 16s ribosomal DNA by PCR, and check their PCR results by gel electrophoresis.

DNA samples are next sent to the university's Genetic Resources Core Facility , where scientific staff, in the DNA Analysis Facility, prepare the DNA templates for sequencing, and load the completed reactions onto an Applied Biosystems 3730 Genetic Analyzer.

The past few years have seen some changes in this process. Data used to be retrieved by logging into an FTP site that allowed anyone to access data from any investigator.

In recent years, this JHU core facility obtained a Geospiza Finch Server, so now, instead of using an FTP site, they upload experimental data, in the form of electropherogram files (aka chromatogram or trace files), into a secure system (the Finch Server) for analysis and delivery. Students can log-in, but now they can only access student data. During the past two years, almost 500 JHU students have logged into the Finch Server to retrieve and view their data.

In the next part of the project, students use BLAST (and our BLAST for beginner's tutorial) to query GenBank at the NCBI and determine which bacterial species were isolated.

All about Phred
One issue that comes up, though, is the quality of the data. Data quality can be a problem when students do PCR for the first time in a lab class. The image below shows a screen shot from a Finch Server illustrating the distribution of high quality and lower quality data from this year's set of 87 chromatograms.

You can see from the histogram that about 20% of the chromatograms have fewer than 50 high quality bases. We're defining high quality, as base calls with a Phred score greater than 20. Phred, KB, and TraceTuner are programs that measure the probability of an incorrect base call. A Phred score of 20 corresponds to a 1% chance of a base-calling error.

What this histogram fails to show, though, is how the high quality bases are distributed in a DNA sequence and where they're located. The Finch Suite has programs that will trim poor quality regions of a sequence, but sometimes its still nice to see what your data look like.

I want my FinchTV
In the next step, students look at their chromatogram data in yet another Geospiza program, available for free, called FinchTV. As you can see, below, they select the high quality region of the sequence, and they can query different databases at the NCBI, just by choosing BLAST sequence.

(Warning potential bias alert: I do work for Geospiza, but I still think this is of cool!).

Through this process, students learn, first-hand, about the diversity of microbial life in the campus all around them and the genetic code that's used to store information in DNA. They also learn about DNA sequence analysis and bioinformatics. Since many of these students plan to attend medical school, this lab serves a critical need in acquainting future doctors with molecular diagnostics.

Both the Finch Server and the core lab staff in the DNA Analysis Facility were important for success of the project. "We never could have done this without the advice and help we got from the people in core lab," said Dr. Rebecca Pearlman, course instructor, "We were able to get our data, talk about quality, and complete a BLAST search in a single class period."

Pearlman adds, "Our students relish the opportunity to do genuine research. They get really excited when they learn they're using the same techniques for bacterial identification that are used by the public health departments."

Of course, I'm writing about this, partly because I get to help out, too. We're making custom BLAST-formatted databanks from each session of the course, so we can do quick comparisons between different data sets, among other things. Over time, these data will allow students at JHU to study changes in bacterial composition from year to year.

And who knows? There are loads of bacteria in every little bit of dirt. What could be cooler than discovering a new species in your first quarter of college biology?

Subject: Classroom Activities

technorati tags: biology, DNA, genomics, microbiology
science education

Experiments on Peeps

2006-02-15T09:40:00.000-08:00

Science fair season is getting close and it's time to come up with interesting experiments that can be done at home. My youngest child wants to do some kind of psychology experiment with the cats, but I'm more intrigued with the idea of experimenting on peeps.

Much of my peep inspiration comes from Peep Research .

After all, haven't you always wanted to know about the biochemistry and anatomy of these simple almost life forms?

Where else can you go to find out the answers to those really troubling questions, like:

What happens when you autoclave a peep?

or drop it into sulfuric acid?

or maybe, drop it into liquid nitrogen?

And what about peeps in space? (or at least in a vacuum?)

Sigh. Some days I do miss having all those lab toys at my disposal.

I guess we just have to be more creative and see what sort of peep tests we can conduct around the house.

Subject: Silly items

Pacific Northwest ASM meeting

2006-02-14T15:54:00.000-08:00

If you live in the Pacific Northwest and want to learn more about microbiology, my alma mater is hosting the:

2006 Northwest Branch Meeting of the American Society For Microbiology
March 10 - 12

It's very affordable for those of you who are teachers and it's even on a weekend!

I'm biased, of course, but I think the meeting will be very informative and lots of fun!

There are some fascinating topics on the agenda.

Microbes, after all, were the first forms of life on our planet and have been voted the form of life most likely to be found out in the solar system. (Wouldn't that be a good one in your high school yearbook!)

True to form, the meeting will have Roger Buick (Earth and Space Sciences, UW) talking about the Earliest Life on Earth and Tom Quinn (Astronomy, UW) talking about the formation of planets.

Since microbes live everywhere, we'll hear talks on those that live in Squid and those that colonize volcanos (before and after eruption).

Unfortunately, the microbes that colonize our bodies aren't always the best tenants. So we'll get to learn new things about the ones that make us sick and the ones where we're having a hard time getting acquainted with the culture (technique).

Last, there are lots of interesting talks about genomics and computational biology. I'm kind of unlucky, though, my talk is at the same time as Maynard Olson. So, you either get to hear one of the pioneers of the human genome project or you can come hear me.

I'll have cooler slides.

Subject: Announcements

Hunting for huntingtin, part IV: What did you expect to find?

2006-02-13T14:52:00.000-08:00

Hunting for ways to do the experiment

In our last episode, we were stopped in our tracks by some glutamines that were missing from our positive control. Sometimes it's hard enough to find the sequences we want; when the sequences are intentionally hidden, it's impossible.

We trudged onward, though, and identified the problem. All we had to do was to turn off the option to hide low complexity sequences and lo and behold, we found our glutamines ... at least we found them in a match to the positive control.

Next, I tried searching with a sequence of ten glutamines.

What did I get?

Nada.

Does that mean GenBank is devoid of proteins with 10 glutamines?

No. In this case, absence of evidence is not evidence of absence.

Huntingtin has at least 10 glutamines and sometimes more. Just because I didn't find a match, doesn't mean that there isn't a match to be found.

Hunting for ways around assumptions

This is a good time to talk about assumptions.

We've learned how to turn off the low complexity filter, but it looks like we will need to do a bit more. I've found this technique to be helpful before and we're going to have do it again. We're going to have to think like programmers in order to guess what assumptions were made in setting up the blastp web form at the NCBI server.

The most important assumption is given here:

To assess whether a given alignment constitutes evidence for homology, it helps to know how strong an alignment can be expected from chance alone.

From "The Statistics of Similarity Scores"

It appears that the BLAST server forms at the NCBI were set up with the assumption that most people would use the collection of BLAST programs to look for homologous sequences.

Homologous protein or nucleic acid sequences are defined as sequences that share a common evolutionary origin. If two sequences are sufficiently similar, according to the statistical parameters in a BLAST search, they are likely to be homologous – that is they are likely to have been derived from a common ancestor. Naturally, the people who set up the web server at the NCBI made the assumption that this is reason why biologists would come to site to do BLAST searches.

There you have it.

The most commonly used set of bioinformatics programs, in the world, (outside of Microsoft Excel), work by calculating the probability that two sequences are related through evolution. (If you have problems with evolution, you probably want to look for another field. Take my advice; bioinformatics will not be a good fit.)

Because the BLAST web form was designed with the assumption that we're looking for statistically relevant homologous sequences, features like low complexity filtering are carried out by default. Low complexity sequences can be found in lots of proteins so their presence would not indicate a common evolutionary origin.

But that doesn't mean that we're not interested in finding them.

We have our own reasons for hunting, so what do we expect?

We are doing this search for an entirely different reason. We're not trying to use statistical significance to support the case that proteins with lots of glutamines share a common evolutionary ancestor. We're using BLAST as a surrogate for Google. We just want to find other proteins with polyglutamine sequences and see if those proteins share the characteristic, like huntingtin, that a genetic disease occurs when we have few extra glutamines.

Right, but how do we find those proteins with extra glutamines?

We go back to the blastp web form and look more closely at the default parameters.

Looking below the set of filters, we see that the default parameter for the Expect (E) value is set at 10. An E value of 10 means that we would expect to find 10 sequences that matched, if we searched a big enough database and it was filled with random sequences. When the cutoff is set to 10, any matching sequence with a value over 10 would be hidden.

Hunting with blastp and to heck with the statistics!

To heck with statistical relevance! I want my sequences!!!

I arbitrarily raised the setting on the E value to 50. A stretch of 10 glutamines is pretty short, and so we would expect to get a high E value even if we have perfect match. (A quick explanation of E values.)

This time, I got results. Over 3400 protein sequences matched my 10 glutamine query.

And check this out:

The best match has an E value of 33.

This explains why I didn't see any sequences match when the cut-off value was set at 10.

But how good a match was this, anyway?

Look at the results:

It was a perfect match.

Sometimes digital biology can be just like working in the lab. We spend lots of time just trying to get our controls to work.

Next time, we WILL do some experiments.

In the meantime, if you'd like to skip ahead, here's your assignment:

Find out if there are other cases where extra glutamines are linked to genetic disease.

And for extra credit - explain why this might be so. Use evidence to support your hypothesis.

Read the whole series:

Hunting for huntingtin, part I Background, reviews, biochemistry of glutamine, and a bit of comparative genomics

Hunting for huntingtin, part II In which we're reminded that database searches are experiments, too.
Hunting for huntingtin, part III Our continuing search for proteins with polyglutamine
Hunting for huntingtin, part IV: What did you expect to find?
Hunting for huntingtin, part V: BLASTing on forward

Subject: Doing biology with bioinformatics

technorati tags: biology, genetics, DNA

Plants that make crystals that look like plants

2006-02-10T16:31:00.000-08:00

Chemical & Engineering News published this fascinating article called "The Secret Life of Plant Crystals" with some wonderful photos of calcium oxalate crystals. These crystals are produced by special cells (called "idioblasts") and the shape of the crystals is unique to each plant.

No one knows exactly why plants make these crystals and the crystals could serve multiple functions. Some of the sharp, needle-like, crystals might help defend plants from being eaten. Some crystals might bind heavy metals or harmful substances and keep them in kind of a molecular toxic waste containment center.

The best feature of this story, though, is the gallery of photos. The Botanic Crystal Fashion Show is composed of excellent pictures, all taken by Harry T. (Jack) Horner at Iowa State University. It's well worth taking a look.

Subject: Web resources, Plants

technorati tags: biology, plants

Multiple views of integration

2006-02-10T13:52:00.000-08:00

Here are some snapshots from one of our favorite friendly phage. Yep, lambda phage, scourge of E. coli everywhere and decades-long friend to molecular biologists.

I used to spend lots of time with shoelaces and bits of string trying to understand how lambda got cut apart, how the E. coli chromosome got cut apart, and how the four free ends, with two strands of DNA at each end, got joined back together. The process of lambda integration is also intriguing because of the way the genes get flipped around during integration, setting up a new gene order.

Now, we're luckier. We get to see and interact with colorful images, derived from the coordinates of the lambda integrase protein itself. The image below shows the two subunits of lambda integrase, colored in blue and purple, hanging on to three different strands of DNA (green, brown, and grey).

In the next image, I zoomed in and hid the integrase protein, so that I could get a closer look at the DNA. This image shows where the integrase protein has cut one strand of DNA so there are two free ends.

Exploring DNA Structure has over 70 structures like these with DNA molecules alone or DNA molecules bound to proteins, anti-tumor drugs, or other substances. It's truly amazing to hear suprised high school kids say they never knew that working with DNA could be as much fun as a video game.

With resources like these, I don't see any reason why high school kids and college students can't use computers for doing science. Why not learn about DNA structure by working with real data?

Subject: Doing biology with bioinformatics

technorati tags: biology, DNA, genetics, viruses

Part. III Hunting for huntingtin

2006-02-04T20:08:00.000-08:00

Dealing with distractions

It's been a couple of months since our last installment. "Next week" has come and gone, and like Odysseus on his journey back from Troy, we've experienced delays in getting back to the story. We've likewise faced our own distractions from lotus-eaters, sirens, harpies, the dreaded cyclops. A typical holiday season.

We've even had our own trials with Circe's angry father. If you follow the weather, you know that Neptune unleashed his wrath on the Pacific Northwest this month. Some people tough it out and ride their bikes to work anyway. Most of us just huddle down inside our raincoats, grimly clench our umbrellas and double-tall lattes, and try to hang on until we see sun-breaks or spring.

But I saw the sun today, so it's time to get back to our story.

In our first episode, we learned that Huntington's disease results from the presence of extra CAG's (in the DNA), which are translated to glutamines in the huntingtin protein.

In our second episode, we wanted to know why the extra glutamines were a problem. So we looked for structures with extra glutamines but couldn't find them.

Too many glutamines

Then, we decided to look for other proteins with extra glutamines.

Why?

We looked for two reasons.

First, we could learn something about the structure of polyglutamine (a fancy way of saying lots of glutamines) if we could find a bunch of glutamines in a different protein. Earlier, we wondered if glutamines formed hydrogen bonds with other glutamines or other amino acids. The availability of a different structure might let us test that idea.

Second, we know that people with Huntington's disease get sick because of the extra glutamines. Well, if extra glutamines in the huntingtin protein lead to disease, extra glutamines in other proteins might lead to other genetic diseases. This is just plain interesting stuff to know about.

This is why doing science is kind of like living in "Alice in Wonderland." It's easy to fall down rabbit holes.

Down we go!

Last time, we tried to use blastp to search the protein database for proteins with at least 15 glutamines but couldn't find anything.

So, we searched again with the sequence of the huntingtin protein itself. We know that this entire sequence is in the database and it can serve as a positive control since it has to match itself.

It almost did.

But look at the image. The matching sequences are a bit short on the amino end of the protein sequence (this part of the protein maps towards the 5' end of the mRNA).

That's odd.

So I looked at the sequence alignments themselves to see what was happening at the amino end of the protein.

The alignment (above) shows that our Query sequence (huntingtin) begins to match a database sequence (identified as Sbjct) at residue 77.

This begs the question: Why isn't there a match to the first 76 amino acids?

So, I looked up the amino sequence for huntingtin in GenBank. Part of the missing section, from 1-71, is shown below. Q stands for glutamine.

matleklmka feslksfqqq qqqqqqqqqq qqqqqqqqpp pppppppppq lpqpppqaqp llpqpqpppp

My conclusion:

The glutamines were missing from the alignment!

Call out John Wayne; it's time for some troubleshooting

We were unable to match glutamines, even with our positive control.

As with any experiment, if the positive control doesn't work, you need to recheck your procedure and find out if something went wrong.

The answer is on the original page of the web form where we began our blastp search.

Notice the box that's checked, next to the phrase "Low complexity." The default setting with blastp filters and hides low complexity sequences like pppppp and qqqqqq. In general, this is a good thing, but not when we're trying to find proteins that contain those sequences.

(We use a similar kind of program with DNA sequences, too, called "RepeatMasker.")

Testing the parameters
Let's remove the filter and find out if our positive control (huntingtin) will work, now.

You can check this yourself. Either type or copy and paste the accession number NP_002102 into the blastp web form, and uncheck the low complexity filter before you do the search.

We're on our way. Join us next time, when we do an actual experiment!

Read the whole series:

Hunting for huntingtin, part I Background, reviews, biochemistry of glutamine, and a bit of comparative genomics

Hunting for huntingtin, part II In which we're reminded that database searches are experiments, too.
Hunting for huntingtin, part III Our continuing search for proteins with polyglutamine
Hunting for huntingtin, part IV: What did you expect to find?
Hunting for huntingtin, part V: BLASTing on forward

Subject: Doing biology with bioinformatics

technorati tags: biology, DNA, genetics

Subjects

2006-02-02T10:55:00.000-08:00

Announcements Courses, meetings, podcasts, and other events

Birds Biology is not just for the birds

Chemistry Chemistry makes biology come to life!

What's that stuff?

Classroom activities and educational materials available from Geospiza Education

Disclosure statement and good questions to ask about any web site

Evaluating web site information

Digital biology: How do people use bioinformatics resources to learn about biology and discover new things?

Antifreeze for winter weather
Future Shock and Selenocysteine
Part II. Future Shock and Selenocysteine: it's time again to update the databanks
Hunting for huntingtin, part I Background, reviews, biochemistry of glutamine, and a bit of comparative genomics

Hunting for huntingtin, part II In which we're reminded that database searches are experiments, too.
Hunting for huntingtin, part III Our continuing search for proteins with polyglutamine
Hunting for huntingtin, part IV: What did you expect to find?
Hunting for huntingtin, part V: BLASTing on forward
Multiple views of integration
White people are mutants

Education: Random thoughts on education and information about summer courses

Insects Some creepy, crawly things, have their own web sites

Microbiology Closer than you might expect

Plants Green, lean, and sometimes mean

The life and times of a digital biologist

Web resources: Diverse web resources for learning about the diversity of life. These cover biology, bioinformatics, biotechnology, microbiology and more.

Wierd Science and Silly things

Can I be more organized on-line than I am in real life?

2006-02-02T10:51:00.000-08:00

As they might say somewhere:

Some are born to be organized and others have organization thrust upon them.

I fall into the latter camp. The last memes made me aware that it's high time to organize topics into a more comprehensible subject groups.

Oh, the memes bloggers play now

2006-01-30T20:01:00.000-08:00

I'm a bit new to this sort of thing and it still seems to smell like a chain letter.

But instead it's a meme that I was tagged with by Hedwig the owl. It seems easy enough, but I keep thinking that I should emerge from a nice hot bath and find that I've solved a puzzle and can move on to the next part of the contest. Will I get to fly with dragons, swim with mermaids? Maybe during bedtime stories.

Well, here goes:

1. Go into your archives.
2. Find your 23rd post.
3. Post the fifth sentence (or closest to it).
4. Post the text of the sentence in your blog along with these instructions.
5. Tag five other people to do the same thing.

It's hard to believe that I've posted 23 items, but I have. And here's the fifth sentence:

Only, in my case, I'm not a graduate student thinking like a thief, I'm a biologist trying to think like a programmer.

Here's the chain letter part:

I'm supposed to spread this meme by adding some some blogs that I find interesting. Dr. Mom is one, I know what it's like to negotiate who drives to soccer games when you have a late night in the lab (or teaching the lab class). It's always good to know that others share those challenges. Jane is busy out trail-blazing through the computing field, so it seems appropriate to tag her in a blog where I discuss an attempt at thinking like a programmer. Science Goddess wins a tag for letting us know about interesting things going on the classroom. She's not in Seattle, I guess, 'cause I heard our school district has filters that block blogs. The people at Headrush deserve a tag, even with their software-company style title. Not only do they write well about writing, but their stories are fun to read. Last, I think Stew deserves a tag, and a "get well soon" note from all the people searching for Lollipops, lollipops, ooh lolly, lolly, pops.

Subject: Silly items

Don't forget Intimate Strangers debuts Tuesday

2006-01-29T10:50:00.000-08:00

It sounds a bit risque, but nothing gets closer than the microbes that share our immediate residence. They live on our skin and in our guts, and leave no part of personal ecosystems uninhabited.

"Intimate Strangers: Unseen Life of Earth" begins on Tuesday, Jan 31st, with a search for the inhabitants of a larger ecosystem. You too, can join the mission to learn about the first life on Earth.

Getting the podcasts is easy, too. If you have iTunes it's mostly a matter of clicking the link at the MicrobeWorld Radio web site. One of our neighborhood middle-schoolers told me that the equivalent program on Windows, works too.

Check it out! The video podcasts are free and, having been a member of the American Society for Microbiology for almost twenty years (gasp!), I know it's a great organization and well worthwhile looking into.

Subject: Web resources, Microbes

Diversity in science: will we ever see a rainbow?

2006-01-27T19:47:00.000-08:00

It rains all the time in Seattle; we should have plenty of rainbows

But we don't. And the rainbows we do have are getting harder to see. This year, the University of Washington had only 118 black students in a class of 5,000 freshmen (1).

Somewhere, over the rainbow, way up high

These appalling kinds of numbers bring occasional guilt attacks on the scientific establishment and institutions of higher education. They belabor and bemoan the all-white faces that appear in the University classroom. They stomp around and give a bit of lip service to the idea of bridging the gap and recruiting. But, after a few mass mailings to garbage cans around the country and some fancy new web pages, they throw up their hands and declare that they tried but the students are nowhere to be found.

Whatever the problem, somewhere down the line, someone isn't trying hard enough.

The Seattle school district enrolls roughly 46,000 children (2, 3), shouldn't we be able to find more than 118 black kids, who want to go to UW, in Seattle alone?

Let's do the math. Only 41% of the kids enrolled in Seattle schools are white; 22% are black (2). With a few crude estimates, we can calculate that, if 1/13th of the kids in the district graduate every year (probably a high estimate), and 22% are black, that would be almost 778 black kids. If even 25% of those kids were eligible for the UW, that would give us 194, or almost 200 black freshman, almost twice as many as the number that started at the UW this year.

Of course, even if all 194 potential black freshmen did go to the UW, only some would major in science. Still, if we don't start filling the pipeline, there will never be rainbows appearing in the lab.

What happened to all the black students from Seattle?

Maybe we could find out by working backward. We know students are more likely to get accepted into college if they take challenging courses in high school. That makes sense. So black kids should take challenging courses in high school, right? Got it. But do they? Can they?

It all depends on middle school.

Entrance into advanced high school courses requires that a student must do well on the eligibility tests. Entry into some of the science programs, like the acclaimed biotechnology academy at Ballard High School, requires that a student be eligible for advanced math.

That makes sense, you need to know math to do science. All kids have the same opportunity to take the advanced math in middle school and learn the material for the test, right?

Wrong.

As a parent of a Seattle middle schooler, I've become acutely aware that kids can get recommendation letters from their teachers, meet the standard on the WASL, and place above the 97th percentile on the math portion of the Iowa Test and not be able to get into honors math in middle school because of limited space and a single Spectrum test. (Spectrum is an advanced program for kids with above average intelligence. Achieve is the McClure Middle school version of Spectrum. Seattle has another special program for really smart kids (APP) but I won't discuss that here.)

Blocking the rainbow from view

Part of the problem comes from block scheduling. Since kids are grouped in schedule blocks as Achievers or non-Achievers (is this a slight language problem or am I imagining things?), they cannot take advanced math unless they score well on all portions of the Spectrum test.

In one fell swoop, kids who are weak in spelling but strong in math are rendered (potentially) ineligible for advanced high school math programs. Kids can catch up. At least one of eighth grade teacher is trying to help, but why not let kids who want to take advanced math, take advanced math to begin with? Why leave kids bored and hanging and make them repeat 4th and 5th grade math all over again?

If kids could take one higher level class, rather than the double-barreled, homework intensive, combination of Achieve Language Arts and Achieve Math, maybe more kids could enroll in one or the other. Maybe this option would even minimize some of the stress and anxiety that some kids in the Achieve program experience.

Oops, you're at the wrong end of Spectrum

Honors math at McClure Middle School, and most likely other Seattle middle schools, as well, is mostly limited (at least in 6th grade) to kids who are in Spectrum. If there is space, after filling the class with the Spectrum kids and kids who do well on the Spectrum test, other kids are allowed to join the class. Most of the kids, though, come straight from Spectrum classes in elementary school. Those kids, who are already in Spectrum, do not have to take a test. They are automatically in. As for the kids who do take the test, it gets more challenging at every grade level. The 5th grade version is far beyond than the test most Spectrum kids took in kindergarten.

Non-Spectrum kids have an opportunity, but only if there is space. Spectrum kids automatically have first dibs on all spots.

What's the problem? you might ask. Don't all kids get an equal chance to be in Spectrum?

Why is Spectrum at one end of the rainbow?

Let's continue our journey back in time and see what we find.

How do kids get into Spectrum in the first place?

The Spectrum track begins in kindergarten. Sometime in October, only a few weeks after school begins, really savvy parents fill out an application to have their kids tested for Spectrum. Once kids are in the program, they stay in.

Most of the kids are tested before they can read?

Right. The kids are tested in kindergarten.

Don't all kids take the test?

No. Kids only take the test if their parents know about the deadlines and they apply for it. If a family doesn't have a stay-at-home parent who can attend school meetings and volunteer at the school during the day, they might miss this bit of insider information. Some Seattle PTAs even hold their meetings during the day, when it's more convenient. Like the fraternities of old, some modern day PTA's could be called the secret societies of the school system.

Roughly half of the kids who attend McClure live in single parent households (3). Needless, to say, those single parents are probably not staying at home. It would be interesting to know how many of those kids ever took the Spectrum test, in kindergarten, or later.

Other parents have commented that kids in the middle school version of Spectrum (called "Achieve" at McClure) are almost all (if not all) white; where slightly over half (51%) of the kids at McClure not. It seems plausible, to me, that at least a few of the 100 non-white kids in the McClure 6th grade class, might be interested in advanced work, if they had an opportunity to try.

Aren't teachers supposed to encourage students to take the Spectrum test?

Maybe, but I've never known this to happen. I have two children in Seattle schools and I've never seen high scores on the ITBS, or Direct writing assessment tests, translate into recommendations to try Spectrum. I saw quite the opposite. High stakes WASL testing and No Child Left Behind are a strong disincentive. No elementary school wants to lose a kid who might pass the WASL.

Elementary schools are also friendly nurturing places. Not all parents (or kids) want to change elementary schools, even if it means the opportunity to be in Spectrum.

Still, parents have a few years to figure out that Spectrum tests are in October and if kids miss the test one year, they can take a harder test the next.

In fact, some kids do exactly that. There are parents who have their kids take the Spectrum test every year, as a matter of practice. These parents may opt to keep their kids at the nearby elementary school, but they're not going to have their kids face the determining factor for middle school opportunities, unprepared. Especially, since the Spectrum test is the one test that will be used to determine if kids are eligible.

I've heard it argued that the assorted rainbow of kids wouldn't do well on the Spectrum test anyway, even if all kids took the test. Perhaps the non-verbal, kindergarten, version of the test might be fraught with cultural bias and other scary things.

I'm reluctant to arrive at conclusions, though, when the experiment has yet to be tried.

Certainly, it's wrong for the school district to exclude kids from opportunities based on a single test.

But what do we do when there are limited numbers of spots in advanced classes? How do we give all kids an equal chance to work up to their potential?

Here's one idea:

We could tweak the registration system. A limited number of spaces in advanced classes might not be as great a problem if the middle schools could work together. Kids could register for advanced classes in either math, Language Arts, or both, as their first choice (rather than the middle school) and list their middle schools second. That way, if one school's advanced class filled up, kids, who want opportunities, could go to an advanced class at another school.

No doubt there are other, and perhaps better, solutions. Somehow kids who want to work harder and take classes like advanced math in middle school should have that chance.

After all, it's sure bet that if you don't take the opportunity to look, you'll never see a rainbow.

References
1. Nick Perry "Bigger black enrollment still only a dream for UW"
Seattle Times, Jan. 16th, 2006

2. Washington State Report Card. Accessed Jan 27th, 2005.

3. Seattle Schools, 2004 Demographic Survey, McClure Middle School Accessed Jan 27th, 2005.

Subject: Education

technorati tags: education

Time for iMicrobe?

2006-01-25T20:06:00.000-08:00

The American Society of Microbiology is doing Video PodCasts! If that isn't cool, I don't what is.

I'm really glad to see the microbiologists taking the lead in reaching out the public with cool new technology. My 11 yr old daughter showed me how to subscribe to podcasts and watch them with iTunes. Now, I'm all set for next week when the fun begins. (We also had a good language lesson, too, i.e. define the word "explicit." Luckily, at 11 she's not likely to search with that term and since she was properly horrified, she immediately deleted all the explicit podcasts that she'd already downloaded to her computer).

For years, I suffered as my husband and I took the kids to see IMAX movies on subjects like beavers, coral reefs, space, Mount Everest, and Jane Goodall. The kids were always a bit puzzled. How come scientists in the movies go to interesting places?

Yep, here's the rest of it: but you and dad sit in the office with computers?

Right. We don't even do cool things like run gels anymore or play tricks with pH indicators and dry ice. This change of venue is too bad in some ways. Our kids would enjoy the lab now and we wouldn't be so paranoid about bringing them through the door. When they were younger, our respective laboratories were places of peril filled with brightly-colored attractive boxes of radioactive waste and interesting glass objects always stacked precariously next to the sink.

So, I was really excited a few years ago when ASM debuted the "Intimate Strangers" documentary on PBS. And really disappointed when the children pronounced it "boring."

I liked it, but even a friendly coccus with sunglasses didn't interest the under 10 set.

Now, there's another chance. We've subscribed to the videopodcasts. When they begin on Tuesday, Jan. 31, we'll be ready.

Subject: Web resources, Microbes

Biotech Expo - coming in March!

2006-01-25T14:46:00.000-08:00

Bootstrap analysis wrote a wonderful story capturing the essense of a middle-school science fair. Now those of you in the Puget Sound will get your chance to see science in the trenches.

Biotech Expo happens March 6th at the Meydenbauer Center in Bellevue, Washington.

I know that's a few weeks away still, but some us need more advance notice than others.

The Biotech Expo is a wonderful sort of high school science fair where students do amazing things like present their own research, sing about telomeres, design web sites, perform skits related to biotechnology, and exhibit works of science art. It's great fun! True, it's a bit more advanced than a middle-school fair, but it's equally entertaining.

The Northwest Association for Biomedical Research has taken on the mission of organizing the Expo and recruiting judges. If you would like to help out or simply want to attend and learn what kids in Washington can do in biology, it's great fun and you might even learn something.

Subject: Education

Thinking like a programmer, searching like a fool

2006-01-22T18:17:00.000-08:00

A recent news report told the story of a woman who was robbed and lost her entire thesis project because it was on a memory stick in her purse. The sensible part of me cringed when I read that she didn't have her master's thesis backed up somewhere on a hard drive, but the other part was intrigued by the way she solved the problem. She found her thesis in a green dumpster by trying to think like a thief.

I have to admire her method. I can make better guesses about searching for things, too; when I try to think like I'm someone else. Only, in my case, I'm not a graduate student thinking like a thief, I'm a biologist trying to think like a programmer.

This approach doesn't work with everything. Like, why do GenBank records give the mRNA size in basepairs? And why do so many people think "data set" is one word? And why does the chicken cross the road?

Some questions just don't have a good answer, no matter how you think about them.

Nevertheless, it does seem that programmers use one kind of logic and biologists use another. Neither is ideal, but thinking like a programmer can help when you encounter puzzling results with bioinformatics tools. Microbes and biological systems may follow biological logic, but web server applications and software packages follow logic of a different kind.

One of these unexpected moments arrived just the other day. I began my quest at the strangely-named OMIM database by searching with SOD1. (I say "strangely named" since OMIM is a database of human genetic disorders, not just those found in men.) Notice below, in the image, the link, creatively named "Links," on the right-hand side of the page.

Normally, I ignore Links since I use Safari (by default) and clicking Links doesn't do anything. But for the sake of completeness, I thought I should give Links a try, so I opened the page with FireFox, clicked Links, and selected PubMed. Then I sorted by Date and looked at the results.

Whoa!

Those results couldn't be right! The most recent paper was dated 2004. Surely people are still researching ALS and publishing articles on SOD1!

My biologist's intuition was piqued. Naturally, I redid the experiment under slightly different conditions. This time I searched for SOD1 directly from PubMed. I found articles in PubMed that date a couple of weeks in the future.

Why were the PubMed links from OMIM so far behind?

Time for another experiment.
What would happen if I chose Links again, but started from a different database?

This time I found SOD1 in the Gene database and selected the PubMed link from collection in the side bar. Now, the most recent paper was from Oct. 2005. Still a bit behind, but closer to current than 2004. You can see the results from all three searches below.

As a biologist, results like these are really kind of disturbing. I expected (erroneously) to get the same results no matter where I started searching. Could this be a problem with link rot? Not link rot at the NCBI! With my biologist hat firmly on my head, I did another experiment to look at Links to a database other than PubMed.

Links to Structures
This time I clicked Links from OMIM and chose the Structure database (MMDB). Only four structures appeared for SOD1. Searching directly from the Structure home page, I found 19 structures. Very worrying. Worse yet, I've used this method! : (

A quick flashback to software testing
Sometimes I get recruited to help out with software testing. These episodes give me the opportunity to read interesting test plans with puzzling questions that ask if the program showed the expected behavior. (Expected by who, I wonder?) Needless to say, it's not always the behavior I expected to see (thinking as a biologist, remember) even though it's often the behavior expected by someone.

That night, I had strange dream about previewing filters and running lost through large pipes and complicated pipelines. In the morning I decided to tackle the problem by thinking like a programmer.

Maybe the software was working the way it was supposed too. Maybe there was another explanation and I didn't do the experiment that I thought I did.

Could I test that?

Fortunately, yes. Clicking the Details tab in the PubMed results lets you see the search that you really did, not the search you thought you did.

Here's what I really did:

But what did I search for?

It turns out that a straight search from a database home page, like PubMed or MMDB, occurs without filters. That is, you search all the records in the database and find the ones that match your query.

But, if you begin searching from a different database, like OMIM and you select Links, you see the world through a database-colored filter. Instead of searching of all the PubMed records with SOD1, you only search the subset of PubMed records that are linked to OMIM.

Rather than searching all the records in the PubMed or Structure database, with SOD1, as I thought I did, when I chose Links from OMIM, I searched a filtered database with only 1% of the records from PubMed (147,450 out of 15,896,470).

The take home message
Links did behave in (what I assume) was the expected way. (I wish I hadn't sent that bug report! Sorry!)

It just appears that no one has added any PubMed or Structure references to OMIM for the past couple of years.

Did anyone expect that?

Subject: Life

technorati tags: bioinformatics, DNA, OMIM

Instructions in ethics for instructors

2006-01-18T13:23:00.000-08:00

Every now and then I read laments about student plagarism and the problems with increasing amounts of information floating about on the web. I suspect that some of the problems might result from college students modeling the behavior that they see from their instructors. Even things that are done with the best of intentions, like copying parts of books for students to save them some money, might be misconstrued by the students as examples of acceptable behavior. If their teachers do it, it must be okay.

So, I've compiled a set of ethical guidelines for college instructors. Feel free to comment.

Ethical guidelines for college instructors

If you use lecture notes that you found on the Internet, ask the author for permission before removing someone's name and posting them on the net yourself.

(After all, you never know when the original person who wrote them will discover them posted on the Internet under your name or get the spam mail about the new course from your organization. It happens.)

If you use materials that someone else developed, credit the source. If you make modifications, you can always say, "based on an activity by so and so."
(Many people have done this with materials that I wrote. Thanks!!!! I always appreciate this.)

Do not retype instructions from a book that you purchased so that you can avoid trouble from the school copy center.

(One instructor, that I worked with, used to give students a 30-page handout that I thought was a pretty impressive piece of work. As least I was impressed until I looked at the lab manual we were using and realized that her hand-out was identical, down to the word.)

Materials can be copyrighted even if someone forgot to put a statement to that effect at the bottom of a web page.
(Believe it or not, this rule comes from an audience question at a conference where I was invited to speak. One of the attendees had compiled an interesting curriculum from materials they found on the Internet. They were surprised and miffed because a program officer told them they couldn't just put other people's materials on a CD and sell them overseas, without permission from the authors.)

Assume that everything you didn't develop is protected by copyright. Images are copyrighted too, unless it's explicitly stated that they are not.

Materials that are developed at a college are governed by the faculty agreement at that college. If you are paid by the college as a contractor, the college may own the materials that you develop.

Even material produced by companies should be considered copyrighted.
(I have found that some people in education apply different ethical standards to crediting academic materials and things that they use from companies. I had the amazing experience of asking an outreach educator why his course web page didn't reference Geospiza as the source for one of our tutorials. They did list sources for other materials. He told me, without even blinking, that they only reference academic groups, and never anything from companies.)

Subject: Education

technorati tags: education

Tangled bank 45 is up!

2006-01-18T06:03:00.000-08:00

Check out the carnival at Greythumb for some wonderful stories on biology, medicine, and education.

In true carnival spirit there's even a Believe it or Not! section with stories that do almost seem unbelievable. Why would people use frogs for pregnancy tests anyway?

Some of the other intriguing topics are:

Internal clocks and Seahawks,

Parasites and plague,

Biology classes and bigger --- well, that's an article on portion sizes, you can fill in the rest.

I can hardly wait to read the story on the Donner party. Or maybe we should call it the party that wasn't.

For those of you new to blog carnivals, the Tangled Bank carnivals are wonderful collections of science stories. Watch out! If you enjoy reading about science, the stories can keep you away from work for a long time.

Subject: Web resources

iSpecies and Google games

2006-01-11T10:01:00.000-08:00

This morning I read about a neat tool, in a BioIT world update, called iSpecies and couldn't resist giving it a try.

The idea of iSpecies, and the possibility of gathering all kinds of information together on a single page for any species, is really appealing and I'm looking forward to further development. You can read the story behind it at the iSpecies blog.

When iSpecies is a bit further along, I think it will be great. Right now, though, iSpecies is more like a new kind of Google game - except maybe funnier.

Here are the results from two searches that I did.

First I searched with Finch and got these results:

Yikes! Imagine if Darwin had seen those guys flying around the Galapagos islands. No one would confuse those finches with magpies. I'm not sure how the articles relate to finches either. Maybe I'm just not ready for the semantic web.

This worked a little better when I searched with Penguin. I'm not sure how the documents relate to penguins but this time the search found a couple of real penguin images and some drawings of Tux. Surely, the Linux guys will be pleased about that. That penguin with teeth is a bit much, though. I'm going to have scary dreams about that one.

Maybe next time I'll try the latin names.

Subject: Web resources, Birds

technorati tags: biology

DigitalBio wins Red Hot Blog of the day

2006-01-06T10:41:00.000-08:00

I don't know much about RedOrbit but I guess Discovering Biology in Digital World was chosen as one of their Red Hot Blogs of the Day.

Here's my award button:

I guess they liked Every Structure Has a Story. It's about amazing DNA structures and the fun I had researching wild DNA for the Exploring DNA Structure Instructor Manual.

It must be true, I read it on the Internet!

2006-01-04T14:01:00.000-08:00

Wikipedia vs. Britannica
Nature recently published a special report comparing the accuracy of Wikipedia, the on-line encyclopedia, with the Encyclopedia Britannica. Surprisingly, the Nature researchers found that accuracy of science entries in Wikipedia is close to that of Britannica. To me, the most interesting part of this finding, wasn't the result about Wikipedia, it was the result about the Encyclopedia Britannica. According to Nature, researchers found that an average science entry in Wikipedia contained four inaccuracies, while the average science entry in Britannica contained three. It's been many years since I looked at an encyclopedia but an average of three errors per article is still higher than I would have predicted.

The telephone game
I think the reason the error rate, in information sources like encyclopedias, is so high derives from the same phenomenon we see when children play the telephone game.

For those of you who never played, the telephone game begins with one person whispering information to second. The second person whispers the information to a third, and so on. The game ends with the last person sharing the (very different) information with the group.

I used to have my students play the telephone game in our Biotechnology and Society class as an experiment to help students understand why newspaper reports on scientific discoveries can be quite a bit different from the original research finding. I would go out in hallway with a student volunteer and relay a couple of sentences that contained the words "AIDS" and "mosquito."

Usually, I said something like this:

The realization in the 1980's that HIV could be transmitted through blood and cause AIDS caused quite a scare. One of the first questions that researchers had to answer was whether or not HIV was transmitted by mosquitoes.

Then I would return to the classroom and send another student out into the hall to retrieve the information from the first. I didn't do a rigorous study but in general, it only took one or two students before we'd all get reports that students had heard that "mosquitoes cause AIDS."

As the informaticists say, spoken information is "lossy." Every time information travels from one person to another, something gets lost.

This lossiness of information even presents problems in places where it really shouldn't. Genetics Home Reference at the National Library of Medicine, is a case in point. GHR provides summaries of information for different genetic diseases found in humans. It's kind of a newer version of the Genes and Disease section at the NCBI. At first I thought this site was really great.

A is for Alanine
Then I found a mistake, quoted below from GHR, in the entry for the SOD1.

The most common change, which occurs in 50 percent of Americans with type 1 amyotrophic lateral sclerosis, replaces the amino acid arginine with the amino acid valine at position 4 in the enzyme. (This mutation is written as Arg4Val).

Well, I've been working a bit with SOD1, both because I know someone whose brother died from ALS, and also because I developed a tutorial for researching genetic ailments with ALS as a model system. So, I was pretty certain that this statement was wrong and that fourth amino acid was not arginine.

To check the statement, I got the reference sequence for the
human superoxide dismutase I protein from GenBank. You can see it below:

>gi|4507149|ref|NP_000445.1| superoxide dismutase 1, soluble [Homo sapiens]
MATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEG
LHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHV
GDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKA
DDLGKGGNEESTKTGNAGSRLACGVIGIAQ

Each letter in this sequence represents a single amino acid. The quote from GHR said that the normal amino acid at position four is arginine (abbreviated R). But the GenBank Reference sequence shows the fourth amino acid to be lysine (abbreviated K).

Well, sometimes the first methionine is processed and cut off of the final protein sequence. If that were true, then the A (alanine) would be the fourth amino acid.

Since the GHR reference stated that a change from Arginine (not Alanine) to Valine was the most common mutation in SOD1, I decided to cross check the information in OMIM, too.

To quote the OMIM record for a mutation at position 4:

Deng et al. (1993) found that the ala4-to-val mutation in exon 1 of the SOD1 gene is the most frequent basis for familial amyotrophic lateral sclerosis (105400)

My guess is that someone on the NLM staff thought (by mistake) that A stands for Arginine instead of Alanine.

Maybe the National Library of Medicine should start a Wiki
I suppose mixing Arginine and Alanine up is a simple mistake but it bothers me for two reasons. First, this is a site that claims a high standard of accuracy, and has a large group of outside reviewers, so even small nitpicky details like amino acid names should be correct. Second, I tried to help out by using the "customer service" web form to let the Genetics Home Reference people know about the mistake. It's been at least a month and I haven't seen the mistake corrected or even received an automated response saying that they got the information.

Alright, we all make mistakes from time to time (yes, me too!) and Wikipedia isn't perfect. The advantage of Wikipedia and other wiki sites, though, is that they can draw on larger numbers of people to help review and correct misinformation. Rather than ask for detailed reviews from a small number of busy people, who might easily miss this sort of detail, a genetic information wiki could, in theory, benefit a larger number of researchers and students if groups like the NLM would allow them to help out.

If the GHR site were a Wiki or had some wiki or even blog capabilities, I would have been able to post a correction, an automated e-mail could have been sent to someone in charge, the posting could be tracked, and someone might have looked at it and checked my contribution. As it is, the information might never be corrected.

I don't want to sound completely negative, because I do like the GHR site. The information is organized well and new conditions are added to the stite on a regular basis. Plus there are links to lots of good sources for additional information. It's just that, now, every time I recommend the site, I have to add a qualifier that students should crosscheck the information with OMIM just to be sure it's correct.

Or maybe I'll just advise them to use GHR for the link list and read the review at GeneTests instead.

Articles referenced:
1. Jim Giles. Internet encyclopaedias go head to head. Nature 438, 900-901 (15 December 2005) | doi:10.1038/438900a

1/17/2006 PostScript: I guess it's not just GHR that's a little off sometimes. I just realized that size of any reference mRNA sequence, in GenBank, is given in bp (base pairs). Sigh.

Subject: Life

technorati tags: education, DNA, genetics

Evaluating website information

2006-01-04T10:15:00.000-08:00

Dr. Hsien Hsien Lee from Genetics and Health has proposed that all science bloggers have an obligation to answer 10 questions that she derived from 10 Things To Know about Evaluating Medical Resources on the Web, a web page from one of the NIH institutes, The National Center for Complementary and Alternative Medicine. This provides kind of a disclosure statement so that readers can understand our biases and better evaluate the information in our blogs.

I don't claim to provide any medical information, but I like this idea, so here are my answers.

1. Who runs this site? 

Part of the answer is Blogger, a free (so far) blogging service owned by Google.

The other part of the answer is that I run the site since I write the content. My Ph.D. is in microbiology and I've been involved with digital and molecular biology and biotechnology for about twenty-five years, both as a researcher and tenured instructor in a community college biotech program. I currently divide my time between developing instructional materials and doing a bit of digital research. If you're interested, you can read more about it in our papers, abstracts, or posters.

Our paper page is labeled "white papers." Not all of the publications on this page are white papers. But I've learned that most people in the software industry do not know or care about the difference between a white paper and a peer-reviewed publication. Definitely a topic for a future blog (or rant?).

2. Who pays for the site? 

Once again, part of the answer is Blogger (and Google) since they provide the blogging tools and site free of charge. But, of course it's more complex than that. The other part of the answer is that I do, by donating my time and writing content. I don't receive any income from the site at the present time, nor does my salary fund this activity.

I think the purpose of this question is to enable readers to determine if a writer is providing unbiased information. To answer that question, since I'm not anonymous, I do have to be sensible about what I write. If I write about Geospiza, or our education projects, my writing will probably have a positive bias. Okay, you've been warned. Read with a critical eye.

3. What is the purpose of the site? 

I started this blog because it provides a quicker and easier way to share information about Geospiza's educational materials and report on our NSF-funded project in bioinformatics education. Geospiza does have an official education section, of the company web site, where many of our instructional materials are located, but it's still easier to post new articles through Blogger.

In summary, the purposes for this site are to:
a. Help students and teachers learn about biology by providing examples that show how biological research can be done with digital tools

c. Disseminate instructional materials from Geospiza's NSF-funded education project and provide information about instructional materials that we've developed and published.

d. Obtain feedback on new materials.

e. Share my humble ideas on science and teaching. ; ^ )

4. Where does the information come from? 

I write about the instructional materials that were developed through Geospiza's NSF education project, my research experiences (some serious and some just for fun), and about research published in scientific journals. Some topics are based on current news. Citations and references are provided wherever I can. When I write about digital experiments and instructional activities, I often provide sites and references so that others can repeat the experiments for themselves.

5. What is the basis of the information? 

This site will discuss my experiences and results plus experiments and findings that have been published in scientific journals. I will do my best to distinguish between objective information and my own opinions.

6. How is the information selected?

Topics are chosen for many reasons. The topics are largely centered around instructional materials and activities but they also derive from my interests, suggestions from others, and questions that people ask.

 7. How current is the information? 

Blogger adds a timestamp to every article showing when the information is posted. Articles that are related to instructional materials are likely to be updated.

8. How does the site choose links to other sites? 

I pick links to sites that I either use for research or simply enjoy reading. The sites that I reference in articles are usually sites that scientists use, like the NCBI. Sites listed in the blogroll are mostly chosen because I enjoy reading them.

9. What information does the site collect, and why? 

I measure web traffic so I can report this information to funding agencies. If you subscribe to our quarterly newsletter, I store your e-mail address. The Geospiza Education e-mail list is not provided to others and you can unsubscribe at any time.

10. How does the site manage interactions with visitors?

Visitors are welcome to send e-mail or post a comment. I do moderate the comments and will not post comments that inflammatory or comments about grow lights, discount pharmaceuticals, refinancing, or developing new and unusual body parts.

Visitors can also subscribe to RSS feeds and/or sign up for our quarterly newsletter by submitting a current e-mail address.

White people are mutants

2005-12-19T11:38:00.000-08:00

50 points for digital biology! Lamason et. al. found a new gene that controls human skin color while studying pigmentation in zebra fish (1).

No red herrings, here! These zebra fish had an unusual golden color that turned out to be an important clue. Lamason and collaborators found that the golden zebra fish lost their normal color because of a mutation in the slc24a5 gene. When the zebra fish have the mutant form, they produce fewer melanosomes.

A short language lesson
Fewer melanosomes, right. What on earth is a melanosome? Melanosomes are special compartments that store pigment, you can think of them like clear containers that hold brown paint. The brown paint would correspond to the pigment, melanin. There also different shades of brown paint (melanin), one lighter (phaeomelanin) and one darker (eumelanin). Melanosomes are only found in special kinds of cells called "melanocytes."

Fewer melanosomes mean a lighter color.

So what do we care about zebra fish??
We're very, very, very distant cousins and we share a common ancestor somewhere way, way, back in time. So, if zebra fish have this gene that controls melanosome production, humans probably have it, too. (Evolution is not controversial in my field; it's fundamental.)

So, just like all biologists have been doing for the past twenty some years, Lamason and friends went fishing off the GenBank (a database of nucleotide sequences), using the zebra fish gene as bait.

What did they catch?
They found the human version of the gene and looked to see if there were any differences that were associated with skin color. Indeed, there were. Europeans had the mutant gene (i.e. fewer melanosomes, lighter skin), while Africans had the gene that makes more melanosomes.

Other research
This isn't the first study to look at the genetics of skin color. Other researchers have run across skin color genes while studying cancer biology. Bonilla, et. al. found a single nucleotide change in the 3' untranslated region of the ASIP gene that is associated with skin color (2). (This changes the sequence of the messenger RNA but NOT the sequence of the protein). One nucleotide is associated with a lighter skin color, in Americans of African descent, with the other nucleotide, the skin color is darker.

The melanocortin 1 receptor (MC1R) also accounts for some variation in skin pigmentation and hair color (3). In this case, variation in the MCR1 protein results in red hair.

What do we conclude?
First, for those of you with a paranoid bent, your worst fears are confirmed. We can tell skin color with a simple genetic test. Hopefully, this ability won't be misused.

Second, the differences that determine skin color are very small. Statistically, it would seem that changing a few nucleotides in a 3 billion nucleotide genome, would be insignificant.

So it would seem.....

Read the abstracts from the original papers:

1. Lamason RL, Mohideen MA, Mest JR, Wong AC, Norton HL, Aros MC, Jurynec MJ, Mao X, Humphreville VR, Humbert JE, Sinha S, Moore JL, Jagadeeswaran P, Zhao W, Ning G, Makalowska I, McKeigue PM, O'donnell D, Kittles R, Parra EJ, Mangini NJ, Grunwald DJ, Shriver MD, Canfield VA, Cheng KC. 2005. SLC24A5, a putative cation exchanger, affects pigmentation in zebra fish and humans. Science. 310:1782-6.

2. Bonilla C, Boxill LA, Donald SA, Williams T, Sylvester N, Parra EJ, Dios S, Norton HL, Shriver MD, Kittles RA. 2005. The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans.
Hum Genet. 116:402-6.

3. Rees JL. 2004. The genetics of sun sensitivity in humans.
Am J Hum Genet. 75:739-51.

Subject: Doing biology with bioinformatics

technorati tags: biology, DNA, evolution, genetics

People who look like their dogs

2005-12-16T17:53:00.000-08:00

Now that the dog genome is done, maybe we need a new project in genetic variation.

What genotypes make people look like their dogs?

Subject: Silly items

Part II. Hunting for huntingtin

2005-12-15T10:04:00.000-08:00

In which we're reminded that database searches are experiments, too.

Playing catch-up with the latecomers
Hi, for those of you who've just joined us, we've gotten lost in some databases while hunting for information on huntingtin. If you'd like to catch up a bit and come back later, you might want to read Hunting for huntingtin (part I).

If not, here's a brief synopsis of the plot and what we've done so far:

learned about Woody Guthrie and Nancy Wexler

found a couple of reviews describing Huntington Disease

got the HD gene sequence and counted the number of CAGs

we learned the CAG codes for glutamine and that glutamine can form hydrogen bonds

Then, we got curious about those extra CAGs and wanted to know if they result from the disease or cause the disease. So we looked up huntingtin at the UCSC genome browser and saw that there are similar genes in mouse, pigs, and zebra fish (plus a few other members of the animal kingdom that were not discussed).

Ah hah! Since mice have a similar gene – and we know that the Jackson Lab is the place to go for all things mouse – sure enough, the Jackson mouse breeders have made mice with extra CAGs, and .....the mice get the symptoms of HD.

So you guessed it, the extra CAGS are the problem, not the result.

As the fearless leader of this expedition, I vote now we look at those extra CAGs a little more closely.

Searching for the lost glutamines
You might remember, in part I, I mentioned looking for 3-D structures with polyglutamine. I did find one structure with a polyglutamine sequence, but it looks like the crystallographers weren't able to resolve the part in the structure where the glutamines are supposed to be. Cn3D shows the missing glutamines in grey in the sequence window. The structure window shows this:

Looking for other structures

Okay, so what can I do? What would you do?

I decided to do a blastp search, since NCBI has this cool new feature where protein sequences, with a corresponding structure, are linked to the structure record in the MMDB.

So I used blastp to search the human protein database with a sequence of 15 glutamines.

What did I find? My result was this: No significant similarity found.

Database searches are experiments, too.
Some of you might be rolling on the floor laughing about now, because you know why I got this kind of result. And some of you might be puzzling over this because it seems kind of contradictory. Didn't I write something earlier about proteins with lots of glutamines? Shouldn't there be some in the database?

Right! Database searches are experiments even if we don't have a pipette anywhere in the room. And there are some fundamental rules for lab experiments that are important to keep in mind.

Okay, Okay, what did we miss?

Close your eyes (oops, no, read the sentence first). Let your mind relax and imagine elementary school science lab. What were the important things to remember about doing experiments?

Disinfect your bench before you start work?

No, not that!

Controls??

Yes.

Experiment Rule 1. Always include control samples, usually both positive and negative.

Personally, I find positive controls to be the most important for database searches. But if I were testing a new program, I would include negative controls, as well.

So I went back and repeated the experiment with a positive control. (I wish this were the only time I've had to do that.) I looked for the huntingtin protein in GenBank and found a reference sequence, NP_002102. And I repeated the blastp search with the reference sequence. (I'm so grateful that I can do this in five minutes on my computer rather than spending a couple of weeks or more trying to get the samples and a couple of days doing a PCR experiment or Southern blot.)

I did a blastp search again. And this time I got a result.

or did I??

There's definitely something odd about this image.

I'm going to stop writing now and give you a chance to solve the puzzle and find out what's wrong.

And yes, this is one experiment that you can try at home. Take the accession number for huntingtin, NP_002102, type it or paste it into the web form for blastp and see if you can up with answer.

Look for more episodes next week in the continuing saga of the search for huntingtin. In the meantime, feel free to post your guesses or results. I won't give away the answer until next week.

As Tigger says, TTFN!

Read the whole series:

Hunting for huntingtin, part I Background, reviews, biochemistry of glutamine, and a bit of comparative genomics

Hunting for huntingtin, part II In which we're reminded that database searches are experiments, too.
Hunting for huntingtin, part III Our continuing search for proteins with polyglutamine
Hunting for huntingtin, part IV: What did you expect to find?
Hunting for huntingtin, part V: BLASTing on forward

Subject: Doing biology with bioinformatics

technorati tags: biology, DNA, genetics

My humble efforts to submit

2005-12-13T20:23:00.000-08:00

Maybe we should just experiment on ourselves
I've come to the conclusion that writing a grant is by far easier than submitting one, at least to the NIH. For the past two weeks, I've been trying to submit a phase I SBIR, and now that we're approaching the second deadline for resolving grant problems (Dec. 15th), it's getting harder to suppress that impending feel of panic as the NIH is insisting that the second deadline is for real.

If you've read other postings here, you might know that I usually write about more teacherly topics, after all, this is not an anonymous blog and there are plenty of sites where you can read writer's rants. However, in light of my current mood of quiet desperation, I really couldn't pass this up. What better way to deal with pain than to try to find the funny side?

A phase I SBIR, for those of you new to the lingo, is a small grant that small businesses can apply for to help jump start new research activities. My company, Geospiza, has had these kinds of grants in the past, so we usually know how to handle these sorts of things. But for this submission period the NIH decided to try a large, uncontrolled, experiment on a few thousand (and probably unwilling) human participants.

That's correct. After a long-standing tradition of voraciously consuming trees by making people send in several photocopies of large applications, the NIH will no longer accept anything but electronic grant submissions. I'm okay with that. It's a good thing to do with the potential to make life a bit easier. The NSF has done this for several years and it works. It's just that the rapid transition, multiple web sites, and lack of useful information on the most challenging site, is making this really, really hard. So, I've decided to share my pain and hopefully spare a few of you from the same path of suffering and anxiety.

Maybe I'm just not the submissive type
I'm optimistic that the bugs will get worked out, but if you plan to submit a proposal in the next year, pay attention.

Do as much as you can in advance. I've spent two weeks now on the electronic submission step and the end is not yet in site. If you do the math, that means at least 4 weeks to write your proposal, two weeks to get it through the proper channels, and possibly two or more weeks to get it submitted correctly. (That's right, at least 8 weeks.)

Don't waste time with e-mailing the commons support group (unless you really don't like looking around web sites for information. The e-mails didn't tell me anything that wasn't already posted.)

Do call the help desk, but be warned, the toll-free phone number is only on the front page of the commons, you won't find it by clicking the Tab labeled "Help." Help is most helpful when nothing's gone wrong.

Stock up on crossword puzzles or some blogs to read while you're waiting on the phone.

How long must I submit? My personal odyssey

Weds., Nov. 30th, 8-11 pm

First let me say this: I use a Mac. Many people groan when they hear that and decide right away that I'm a stereotypical troublemaker and that all the problems are due to my poor titanium G4 laptop. So, usually when I need to ask for help, people want to blame everything on my Mac. But my Mac is not the problem. I've learned to adapt when it's necessary. And just in time, too, since the NIH has decreed that we shall all use either Windows or Virtual PC, if we wish to apply for funding. So I began the odyssey by installing the government-mandated PureEdge program on Virtual PC my Mac. First hurdle, successfully jumped!

Then, I hit the SUBMIT button in PureEdge. Something seemed to happen. FireFox opened up. And then everything stopped.

No luck. I try again, no luck. I notice that the copyright date on PureEdge is a few years old (2002), so on a hunch I open up Internet Explorer and the submission process starts working! Yeah!!! It's submitted. I can go to sleep now.

Thurs., Dec. 1st, 5:30 am AAAHHH! There's an automated e-mail from the NIH saying that there are errors in the application (but no indication of what they are) and today is the deadline and I have leave town tomorrow morning!! Plus, once the grant has been submitted I have two days to log in to the commons and approve it. (This step seems kind of redundant to me since it's quite alot of work to submit something that I don't approve of.)

Really, it would be nice if the subject line in the e-mail said something, like the Hitchhiker's Guide to the Galaxy, in large friendly letters, : DON'T PANIC!.

But that would be wrong. Panic is exactly what's called for in this situation. Among the helpful bits of information in the e-mail is the statement:

To view the messages, log in with your username and password
to the NIH era Commons website at .... Then select the Status menu item, retrieve the grant application, and click on the Application Identifier (TN) link next to the submitted application.

And a bunch of other stuff that didn't really matter because I logged and couldn't find my grant application. Naturally, I couldn't retrieve it.

I e-mailed the help desk but then got nervous and called support. Ah good, only 8 people in the queue. The nice and very cordial support person told me the problem was that my user name was missing from the proposal. Was that in the instructions? I added my user name and uploaded the grant again, guessing from the time stamps on the e-mails that it would be about 8 hours before I would find out if this worked.

Thurs., Dec 1st 7 pm I get another e-mail with the same error message as before. I still don't see my grant when I log in but at I'm a little relieved to see that the deadline for corrected applications has been extended to the 8th (of course we have to have a written note from our parents .. no just joking, but we do have to include a cover letter with an explanation for why the proposal is late, I kid you not!). And I have to catch a shuttle at 5 am to get to the airport to go to California and give a professional development workshop for high school teachers on using computers for doing biology (yes, you sense irony).

This time I sent an e-mail to the support group asking for their help.

Tues., Dec 6th I'm back in town and at 11 am receive a return e-mail from the commons telling me to log in and retrieve the grant (that I can't find or see) with a list of the most common problems and a nice note stating that my issue has been closed.

Okay. I get on the phone once again (only 20 people in the queue this time!) and once again talk to a very nice, patient help desk guy, who tells me how to find submitted grants that have errors. He also points out that I'm not a PI! What!!! Okay, I suppose that one must be my fault since I was the person in our company who took the initiative, a year ago, and applied for a commons account in the first place. I don't how I could have done this and not assigned myself a role as a PI, unless I thought I had to have an NIH grant at the time. Never mind that. Help desk guy tells me it's not too late. I can make myself a PI. And bless him, he tells me how to find grants that have e-submission errors so I can find and fix them myself.

Oh yeah, and I need to fix a math error. Rounding up by 20 cents is an unforgivable sin.

No problem. I do it. Except this time, I forgot about the browser issue. I spend two hours trying to figure out why the grants.gov submission isn't working and talking with a very nice (but clueless) person at grants.gov who tells me that our T1 connection must not be fast enough.

Luckily I remembered the solution before someone took my stapler.

Tues., night, Dec. 6th It turns out that I had a typo in my congressional district and apparently the NIH cannot figure out where I live from an address and zip code. Plus, Microsoft Excel cannot calculate 7% accurately. The value was off by 0.000625 cents and that discrepancy triggered more error messages. I fix the errors again and once more I SUBMIT.

Weds., Dec 7th, 1 am I get an e-mail saying that the grant has been retrieved. Yeah! This time it has to work!

Weds., Dec. 7th, 6 am I log in to the NIH commons to check and find out if there's a way that I can see the grant has been received. Nada. I can find the two of the previous grants with errors but not the latest version.

I sent an e-mail to support asking them if I should be able to see if the grant has been retrieved. I can see the others that had errors by using the method I learned from the help desk guy, but not the most recent submission.

I start checking the site on a daily basis.

Fri., Dec. 9th I get a canned answer from support with a list of the most common submission problems. I e-mail a reply that I still can't tell if the grant was okay or not. I try calling the help desk. No luck. But the help desk phone message has morphed into something new and amusing. Along with the usual bit about the call being monitored, I now hear:

"The help desk is experiencing a high volume of calls and not taking any e-mails at this time. If you have left a voice mail please e-mail us at.... If you wish to remain on the line you may do so. If you wish to hang up, press 1 now...." and so on.

Apparently, (to paraphrase the taped message) the commons is experiencing such a high volume of calls that they've lost all their voice mail capacity. You cannot leave a voice mail and if you thought you left one earlier, you were wrong. (Okay, my confidence in the system has been restored.)

I especially like the part of the message where you're told to press 1 to hang up. (huh? The usual method works just fine. I've been doing this every day for a week so I know this).

I send an e-mail to support.

After all this fuss, don't I deserve a little reassurance?

Mon., Dec. 12th I'm getting worried about not seeing the application anywhere in the commons. I spend half an hour waiting on the phone to talk to a help desk person. Time to press 1.

Tues., Dec. 13th I get an automated e-mail at 3 pm from the NIH commons saying:

Our records indicate that you may have started, but not completed, the submission process for an SBIR or STTR grant application to the National Institutes of Health (NIH)..... etc.

Yikes! But at least, I think I know what's wrong. I find something new in the list of submssion problems on the commons website mentioning that I need to edit my account so that I'm both a PI and an SO (some administrative thing). I make myself a new PI account. BUT here's the worst part. TIME IS RUNNING OUT. This is all supposed to be resolved by the 15th and after I set up my second new PI account (with a new user name), I get an e-mail saying that it will take the Commons 2-5 days to verify my account, plus, since I have a different user name associated with that account, which means that I will have to upload the whole enchilada again through grants.gov and the validation process seems to take 8 or so hours.

I am getting very worried about this. I now have 3 accounts with the NIH commons, with 3 different user names and 3 different passwords. And one account with Grants.gov with another set of user names and passwords. And I still don't know where my proposal is.

Weds. morning, Dec. 14th I found a link last night on the era commons web site for sending feedback on the submissions process. I sent a long panicky diatribe and this morning got a very nice e-mail from someone at the NIH. This was followed up by a phone call and some help. It's now 10 am and we're still not done with the process but I'm staying optimistic. I need to resubmit through grants.gov one more time but I'm getting messages that say Bad Gateway. Right bad, bad gateway, you be nice to that upstream server.

wish me luck! I'll keep you posted when I've finally submitted.

FYI: I want to emphasize that both the grants.gov and NIH help desk people have been very nice and cordial throughout this ordeal. Their task is not easy.

Weds. Dec. 14th 5:45 pm It's in and it's done and I owe many thanks to the kind and helpful people at the NIH help desk.

For those of you thinking about submitting a proposal soon, give yourself plently of time, and consider yourself warned!

Subject: Life

The birth of a hummingbird

2005-12-10T10:18:00.000-08:00

A friend sent me this link since I manage the Hummingbirds soccer team. Hopefully, the person who posted these shots of baby hummingbirds will leave them up for awhile.

Update:
My husband told me about this page at Nature Photography with other truly incredible hummingbird photos. There are some great photos of hummingbirds in mid flight plus some pics of hummingbirds sitting quietly at bird feeders. Incredible!

Subject: Web resources, Birds

technorati tags: biology, birds

Hunting for huntingtin

2005-12-09T16:53:00.000-08:00

A bit of background
Alice's Restaurant is a movie with an unforgettable song that mostly revolves around Arlo Guthrie hanging out with his friends. Somewhere in the movie, the conversation turns to Woody, and someone asks the question that no one wants to touch. Does Arlo's girlfriend know about Huntington's? ...dead silence... Now, I did see the movie quite a few years ago, so my memory of the plot is kind of fuzzy but, as I recall, no one in the movie was prepared for that kind of discussion.

It has been a couple of decades, or so, since Alice's Restaurant was made. Woody Guthrie is long dead, but kids still sing This Land is Your Land in elementary school, and people with Huntington's disease (HD) are still without a cure.

HD is a terribly debilitating disease that strikes people in the prime of life and unfortunately, after they're likely to have had children. The disease is inherited in an autosomal dominant manner, which boils down to a 50:50 chance of getting it, if one of your parents has it. All it takes is the wrong copy of chromosome 4, with a few dozen extra nucleotides and you're SOL.

The difference between now and then, though, is that there's a genetic test that can divine your possible fate. A little bit of blood, some enzymes, a way to separate different-sized pieces of DNA, and you can find out if you better go to Disneyland while there's still time or you might want to sign up for that retirement plan that people are always telling you about.

Much of our knowledge about HD comes from work by Nancy Wexler. I was fortunate to hear Dr. Wexler talk about HD and her work with afflicted families in Venezuela. at the University of Washington, a few years back. If you'd like to hear her for yourself, NPR has an interview with Dr. Wexler that's well worth a listen.

Hunting for reviews
Okay, the disease is horrible, but learning about it is interesting. Perhaps we can even learn some general things about biology along the way.

We'll begin by learning a bit about the gene and the disease. Both GeneTests and the Genetics Home Reference at the National Library of Medicine tell us a bit about the disease symptoms, and that the difference between having HD and not having HD is a few extra CAGs in the huntingtin gene. We can even find a lab that will do a test by clicking links at these sites.

We also find out that the HD gene is also called "huntingtin" and is quite large. Huntingtin is over 200,000 bases long and has 67 exons. Plus the gene is quite polymorphic as far as the CAG repeats. Normal people have 10-35 CAGs in the huntingtin gene, where individuals with the disease can have as many as 40-55 CAG's.

Hunting for the gene
To confirm the presence of repeated CAGs, it's nice to be able to find the huntingtin gene sequence ourselves and take a look. If we go to the NCBI, choose the Gene database from the pull-down menu at the top of the page, and type "huntingtin," we get a list of genes that includes the huntingtin gene from multiple species, plus lots of genes for proteins that interact with huntingtin. So we do have to read carefully to pick the link for the right gene.

Going to the HD Gene record gives us lots more info. In the middle of this page is a picture of the introns and exons along with links to reference sequences from the contig (NC), mRNA (NM_00211), and protein (NP002102). We click NM_002111 and choose FASTA to get the DNA sequence that corresponds to the huntingtin mRNA.

Now, we see a long sequence with lots of A's, G's, C's, and T's. How are we going to find the CAG repeats without going blind staring at a computer screen? No problem, we just need a little fancy footwork with our web browser. Most, if not all, web browsers have a way to search for text on a web page. You can find one by looking through menus or use whatever key commands you normally use with Microsoft Word (Mac OS X, use Command + F, for Windows, use Ctrl + F). If you use FireFox, the search feature is really nice. Not only can you find the text, you highlight all places where it occurs. So, with Firefox, our search results look like this:

Hunting in the animal kingdom
Sure enough, a normal huntingtin gene has 19 CAGs (see above) and the disease-related mutant protein has about twice as many. This is unusual but it doesn't tell us why that would be a problem. Do the extra glutamines cause Huntington's disease or result from it?

We might be able to answer this question by looking at HD in other animals. If we search for huntingtin gene at the UCSC genome browser we can find that mice (Mus), pigs (Sus), and fish (Danio) all have the HD gene, too, with the same organization of introns and exons. The exons are the straight lines in the picture below. These are the DNA sequences that get copied into mRNA.

Since mice have the huntingtin gene, maybe mutant mice can help us the answer this question. The Jackson Labs have been able to make mice with the equivalent of HD by adding extra copies of CAG to the mouse version of the huntingtin gene.

If we go to the Jackson Labs site and search for Huntington, we find examples of five mice that develop HD symptoms, when they have extra CAGs. This result tells us that the extra CAGs are enough to spur the development of HD.

Still hunting for answers
The role of the extra CAGs is still unclear but we do know that CAG codes for glutamine.

Since glutamine is able to form hydrogen bonds through the amino and keto groups (blue and red in the picture below), proteins with extra glutamines might cause problems by binding to other proteins and interfering with their normal activities.

I've been unsuccessful, so far, in finding protein structures with more than three glutamines in a row, but I did find polyglutamine tracts in lots of protein sequences and some tantalizing clues in the literature.

So, tune in next week to learn what we can find when we continue our hunting expedition and venture into the deep, deep, darkness of the digital databanks.

Read more of the series:

Hunting for huntingtin, part I Background, reviews, biochemistry of glutamine, and a bit of comparative genomics

Hunting for huntingtin, part II In which we're reminded that database searches are experiments, too.
Hunting for huntingtin, part III Our continuing search for proteins with polyglutamine
Hunting for huntingtin, part IV: What did you expect to find?
Hunting for huntingtin, part V: BLASTing on forward

Subject: Doing biology with bioinformatics

technorati tags: biology, DNA, genetics

Summer courses in digital biology

2005-11-08T11:11:00.000-08:00

For the past three years, Dr. Linnea Fletcher and I have been teaching summer courses through the Chautauqua program funded by the National Science Foundation. These courses are organized on a national basis by the University of Pittsburgh and the Council of Chautauqua Field Centers, and supported by the National Science Foundation Division of Undergraduate Education.

Some of the courses offer the chance to learn about fascinating topics in exotic places, like one course on Galileo that was offered in Italy. But if you can't go to Italy, you might like to come to Texas, where you can learn about digital biology and hear good music in the city limits of Austin. Since our courses are in June and it's too hot to go outside, it's a great time of year to work indoors during the day in an air-conditioned computer lab, and venture out to hear music at night.

It's a bit early, but I'm posting the course descriptions, now, to make more people aware of the courses and gather topic requests. We make changes every year to incorporate new resources and tackle cool papers that we've read. So if you have a topic request, or you attended past courses and want to post rave reviews, please add your note in the comments at the end of the post.

Registration information will be available soon at: http://www.chautauqua.pitt.edu

A Hands-On Tour Through the World of Bioinformatics
LINNEA FLETCHER, Austin Community College and SANDRA G. PORTER, Geospiza, Inc.
Date: June 8th-10th in Austin, TX

High-throughput data collection, web-based bioinformatics tools, and molecular databases have changed the nature of biological research. This course places a strong emphasis on hands-on practice with bioinformatics resources to explore current topics in biological research. Activities and topics in this course are updated yearly in order to incorporate new tools, developments and ideas in fields of genomics, proteomics, and structural informatics. Example topics are: Genotyping, DNA sequence analysis, sequence assembly and alignments, identifying SNPs and other types of sequence variation, genotyping, designing PCR assays, BLAST, making the most of a database search, molecular modeling tools (Cn3D), genetic databases, OMIM, and interpreting experimental results. Lastly, participants discuss how bioinformatics can be applied in their courses.

For college teachers of: bioscience-based courses such as microbiology, genetics, biology, pharmacology, allied health, biotechnology and molecular biology. Prerequisites: none.

Studying Evolution with Bioinformatics
LINNEA FLETCHER, Austin Community College SANDRA G. PORTER, Geospiza, Inc.
Date: June 12-14th in Austin, TX

Students in this course will learn how bioinformatics resources can be applied to the study of evolution on a molecular level. This course includes a significant hands-on component, with new topics introduced every year. Example topics include: genome browsers and tools for comparative genomics, evolution in HIV, evidence for a common ancestor, and looking at genetic codes. Participants learn how to use the UCSC genome browser, prepare a data set, generate multiple sequence alignments, and prepare phylogenetic trees, and use free tools for viewing three-dimensional structures from related proteins. Discussion topics include: choosing sequences for phylogenetic studies, along with different methods for creating phylogenetic trees (neighbor joining, parsimony, maximum likelihood). Topics such as orthology, paralogy, homology, homoplasy, and comparative genomics will also be covered. Case studies where phylogenetic trees have been tested experimentally will also be discussed. Lastly, participants discuss and explore how bioinformatics resources can be used in their courses.

For college teachers of: bioscience-based courses including biology, microbiology, organismal biology, molecular biology, genetics, evolutionary biology, and biotechnology.
Prerequisites: the introductory course, June 8-10th, is recommended.

Subject: Education

Head, Shoulders, Knees, and Toes

2005-11-07T18:54:00.000-08:00

Why is an eye, an eye and a nose, a nose? Why do different cells create different kinds of tissues when all the cells in a single organism start out with the same set of instructions (aka DNA)?

Head, Shoulders, Knees, and Toes is a learning activity that helps students discover, for themselves, that certain genes are expressed in some tissues but not in others. My goal here, as part of our NSF-funded project, is to show how students can learn biology by doing science with bioinformatics tools.

If you already know all about ESTs, you might want to jump ahead and read about the activity. If you don't know what ESTs are, you might want to read a bit of background information first.

A bit of background information
So, why is an eye an eye and a nose a nose? The answer comes from the sets of instructions that are read. Imagine an instruction book for building a miniature city. Now we give 30 identical copies of that book to a class of 30 students and we tell the students to randomly flip through the book and start wherever they like. Some students might end up building train tracks, some students, parks; others, a library. This isn't a perfect analogy, but you can see that the structures that get built are determined by the instructions that are used.

Cells develop their own identities through a similar mechanism. Some cells use the instruction kit for becoming a heart, some read the kidney instructions, and so on. Our instruction book, however, is written in a human-readable language. The language read by cells is written in a chemical code, DNA, with four different "letters" A's, G's, T's, and C's. Our cells read the instructions through a process called "gene expression" where the code is copied first into RNA, and sometimes translated into protein. The end result, in either case, that different kinds of cells are produced as a result of reading different sets of instructions.

Okay, so different kinds of cells develop because of different instructions. What can we do with this information? What can it tell us?

Well, one of the things we do, as molecular biologists, is to try and identify the sets of instructions that are used by different kinds of cells at different times during development, or in response to different signals. We begin by purifying RNA from cells. Next we make a DNA copy of that RNA (this is done for technical reasons because DNA is a more stable molecule), then we determine the nucleotide sequence. At the end of this process, we have a set of DNA sequences that correspond to RNA sequences, from particular types of tissues or cells. We call these sequences "ESTs," which is short for expressed sequence tags. Remember, one of the first steps in reading the instructions, or expressing a gene, is to make a RNA copy? Well, if we find a piece of RNA, it indicates that a gene that was expressed.

Once we have a set of ESTs, we characterize that set to learn more about the cells that supplied that RNA. We can look at the relative abundance of different ESTs to see which instructions are read more often. We can try to identify ESTs by comparing their nucleotide sequences to a database of sequences. We can compare the ESTs produced by different cells to see if some are only found in the heart, or liver, or stomach. And we can look at when ESTs are produced to see if they might play a role in development. Some ESTs are only produced in fetal tissue some are only produced in adults. This can help us understand how our bodies change during our lifetimes. We talk about the production of these bits of RNA as "tissue specific expression" and "developmental specific" expression to indicate that some RNAs are only made in certain tissues and some RNAs are only made at certain times. There are other RNAs that are produced in response to certain signals, like stress or tissue damage, but we're going to pass on that topic for now.

Time to describe the experiment
Okay, but what do ESTs have to do with the Head, Shoulders, Knees, and Toes activity?

In this activity, students are assigned one of 30 unknown EST sequences and asked to find out what the sequence codes for and where and when it's expressed, in addition to a few other facts about the sequence. (You can go straight to the data set or download the pdf from Geospiza's teaching materials)

All the ESTs in this data set correspond to messenger RNAs, so they do all code for proteins. (That sounds obvious but many ESTs in real life are contaminants). They come from many different tissues and from many different creatures including honeybees, pine trees, carrots, humans, lobsters, cats, mice, gerbils, fish, frogs, chickens, dogs, and other living things.

The important feature for this experiment, is that all of these mRNAs show tissue-specific expression, that is, they code for proteins that are only made in certain tissues. Further, some of the sequences are also expressed in a developmentally specific manner.

One of the sequences, for example, codes for a protein that's only made in germinating seeds. Another sequence codes for human tyrosinase, which might only be expressed in embryos and adults.

As mentioned above, students are charged with the mission of identifying their sequence and using evidence and statistical measures to support their identification. All the sequences are at the Geospiza Education web site and there is an animated tutorial that shows them how to use blastn, a commonly used program for comparing nucleotide sequences.

Once students have identified their sequence, they need to find out where the mRNA came from and where and when it's expressed. I found, in giving professional development workshops, that many teachers have never heard the phrase "gene expression," even though it's commonly used in biological research. So, doing this activity helps teach the language of biology by having students explore gene expression in a new way.

Students also get to see something about the magnitude of gene expression.

So how does this work? UniGene to the rescue!
If the NCBI web server is used for a BLAST search, the results include links to other NCBI databases if a sequence is referenced in multiple places.

Both the sequences in these blast results match my query sequence equally well and code for the same thing. One of these is also a reference sequence (NM tells this, but that's another story).

Both the U and E, in the brightly colored boxes, are linked to databases with expression information. U stands for the UniGene database, a set of EST sequences from different tissues. E probably stands for Expression since the E is linked to the Gene Expression Omnibus, which contains lots of data from microarray experiments. For now, I will stick to UniGene and write about GEO in a later article.

If I click the U, in the blast results, and follow the links, I get the UniGene reference for my sequence. If I scroll down a bit on the UniGene page, I see the heading, "Gene Expression."

Clicking the blue "Expression Profile" link takes me to a nice summary table of EST data that looks something like the dot blots we used to do when I was in graduate school. This table loads slowly, so be patient.

The first column has the tissue type, the second, the number of matching transcripts (RNA molecules) normalized to 1 million, then there are digital ovals that look something like a signal from a radioactive probe, and last, the fraction of matching transcripts divided by the sample size.

This table makes it pretty clear where the tyrosinase gene is expressed.

Below the expression table is another digital dot blot organized instead by developmental stages. It looks like this gene is expressed only in embryos and adults, but if we carefully look at the number of ESTs that were sampled in juveniles; it appears that the lack of expression could be a result of the sample size. The EST pools from embryo tissue and adult tissue are at least ten times larger than the pool of ESTs from juveniles, so it looks like we need a much larger sample size from juvenile tissue to get a conclusive result.

How do students learn about biology by doing this activity?
This activity allows students to see for themselves that some genes are expressed in specific tissues and at specific times during development.

Through this activity, students can discover that genes are regulated before they even know how this works. And making discoveries, after all, is the prize of doing science.

Subject: Classroom Activities

technorati tags: biology, DNA, gene expression, genetics, education

Anti-freeze for winter weather

2005-10-28T12:02:00.000-07:00

Winter is coming soon, my bike ride to work was pretty chilly, and it seems like a good time to be thinking about antifreeze. Antifreeze proteins, that is. Antifreeze proteins help keep pudgy yellow meal worms from turning into frozen wormsicles and artic flounder from becoming frozen flat fish.

Funny, but I would have thought that one antifreeze protein would be pretty much like another. I've played with some antifreeze structures before but I never realized that they're more diverse than you might guess. Some antifreeze proteins, like the one from the winter flounder and the sculpin are strictly alpha helical. Antifreeze proteins from yellow meal worms (aka "fish food") however, look pretty rigid and tough, with lots of organized beta sheets and a few random coils.

Who would have thought that two protein structures that seem so different would function in a similar way?

Or provide so much entertainment? I found lots of fun things to do with these structures while playing with them in Cn3D.

I noticed that the sequence of one of the structures contained an unusual amount of alanines (a's). I searched for alanines to highlight them in yellow. Which structure seems to be unusually high in alanines?

Coloring the structures by molecule, with the default rendering, shows some interesting yellow bars. Clicking the structure in the region of the bar, highlights a pair of c's in the sequence. Can you tell which structure contains disulfides?

Another question that springs to mind, in looking at the yellow meal worm protein, is this: what holds those two chains together? The two chains look like they're floating in space.

I know that the two chains aren't bound to each other by disulfides.

So, I asked if the two chains were associated by electrostatic interactions (bonds between positive and negatively charged amino acid side chains) by changing the coloring style to reflect charge. This color scheme shows negatively charged amino acids as red, positively charged amino acids as blue, and those with neutral side chains as grey.

You can download a key to the one letter abbreviations and a diagram of the amino acid structures from our web site:
http://www.geospiza.com/education/materials.html

So, are the two chains held together because of interactions between positive and negatively charged sidechains? What do you think the answer is?

I tried something else. I changed the rendering style to space fill and the coloring style to element.

Now:
oxygens are red,
nitrogens, blue;
sulfurs, are yellow (and so are you)

Ah there's nothing like good poetry (and that was nothing like it)

carbons are grey
and hydrogens are white.
I guess that makes everything quite alright.

We don't see hydrogens in X-ray crystal structures, though, since they're not heavy enough to scatter electrons.

Coming back to the two chains, it looks like the carbons fit together like a puzzle (remember, they're grey?).

I zoomed in for a better look.

The oxygens are lined up on the inside where the two chains interact. I think they might form hydrogen bonds, but remember, we generally can't see hydrogen bonds in crystal structures.

I guess it's time for NMR and a slice of rhubarb pie.

Subject: Doing biology with bioinformatics

technorati tags: anti-freeze, biochemistry, biology, molecule, nature, proteins

Unusual biology on the internet

2005-10-21T11:32:00.000-07:00

As a digital biologist, I spend way too much time on the Internet trying to postpone doing real work (just a joke, really!). One of my work-postponing occupations is reading about things like the Ig Nobel awards. The Ig Nobels reward science that makes you both laugh and think. These are great criteria for awards, since we scientists have a tendency to take ourselves far too seriously. Better yet, the Ig Nobels reward experiments that my kids would like. The award for biology went to researchers who actually smelled 131 species of frogs to see if the frogs were feeling stressed. My youngest child would love smelling frogs. Of course, I don't think we could do a good control experiment; all the handled frogs would be terribly stressed.

Others have already written about the award for medicine, which went to the inventor of Neuticles. These are fake testicles for dogs. Having known one male dog owner who refused to let his dog have the big operation, I think these are probably great for wives of male dog owners who sympathize with their dogs, just a bit too much.

But my favorite award from this year wasn't for biology. It was the literature award. The winners were those most creative e-mail writers, those enterprising Internet entrepreneurs and champions of persuasive communication, the Nigerian spammers. Some people enjoy their work so much they've gone to the trouble of collecting it and posting them for everyone to enjoy, see Scamorama.

Nothing like the continuing adventures from the Lads from Lagos and few sniffs of stressed frog to start the day off right.

Subject: Silly items

It all came out right in the end

2005-10-20T09:46:00.000-07:00

Congratulations to Barry Marshall and Robin Warren for winning the 2005 Nobel prize in Physiology and Medicine for their discovery that Helicobacter pylori causes ulcers. I'm especially impressed with the experiment that Dr. Marshall carried out, drinking a solution of bacteria and giving himself ulcers. It makes me cringe but I'm glad he did it. The posting at the Nobel site has a nice description of the discovery.

Unfortunately, whenever I think about this or describe it someone, my brain insists on really bad jokes. My apologies to Barry Marshall, since there's nothing funny about his work. But ...

"It really took guts"

"He had intestinal fortitude"

"He had the stomach for the work"

"He swallowed the hypothesis, hook, line, and sinker"

"He put his whole self into his work" (or did he put his whole work into himself?)

"He felt in his gut that he must be right"

"He knew those weren't butterflies in his stomach"

Subject: Silly items

Every structure has a story

2005-10-17T10:04:00.000-07:00

It's been a long nitpicky journey but it's nearing the end. The almost-final version of the instructor manual, for "Exploring DNA Structure," has been sent off to the printer and there's nothing I can do now except patiently wait. In a week or so, I'll get to review it one more time in printed form and then release it to the world in November.

My family is quite relieved. For the past few week, I've been in distant space contemplating things yet to be done and obsessing about items that need to get checked off the list. It's gotten so bad that I spend soccer games thinking about margin size or I take the dog for a walk and stop suddenly to tell my husband that I must check the index one last time and make sure that all that chapters are starting on the right side of the page.

It's all worth it, though. I confess I've become totally entranced with molecular structures. They are the most fascinating art form I've ever seen and every structure has its own story. I know because I read and wrote 69 structure stories for the "Exploring DNA Structure" instructor guide. This was never in my original plan but my friend Charlotte Mulvihill wrote to ask me about the functions of different structures. I blithely replied that sometimes the only function was to satisfy the curiosity of the researchers. Then, I started to wonder, too, and couldn't help reading about all of them and compiling an answer guide for the manual.

The more I learned, the more fascinated I became. Some of my favorites are shown below.

Many structures on the CD contain anti-cancer or antiviral drugs bound to DNA. These drugs kill cancer cells by making it hard for cells to copy, unwind, or repair their DNA. Although these drugs harm all growing cells, cancer cells suffer the most damge since they grow more rapidly than normal cells. This image shows tamoxifen, a drug used to treat breast cancer, bound to DNA.

Telomeres protect the ends of linear, eucaryotic chromosomes. Unlike the rest of the chromosome, with double-stranded or duplex DNA, telomeres form four-stranded quadruplex structures with lots of positively charged ions. I think the ions probably shield the negatively charged phosphates and allow the strands to get close together.

DNA can form interesting loop structures where a single-strand kind of twists around back on itself. This structure is thought to regulate expression of the protective antigen gene, in Bacillus anthracis, the bacteria that cause antrax. The protective antigen plays a key role in development of anthrax symptoms. If we can understand how this gene is turned on or off, perhaps we can find a way to turn this gene off and prevent the symptoms altogether.

Recombination intermediates, also known as Holliday structures, are wild. When I was an undergraduate, I found recombination to be very mysterious. This structure shows DNA in the act of breaking and joining to other strands. Seeing the structures makes genetics less mysterious and considerably more fun.

Subject: Classroom Activities

technorati tags: anti-freeze, biochemistry, biology, molecule, nature, proteins

What if Garrison Keillor did bioinformatics?

2005-09-16T11:33:00.000-07:00

Okay - I wrote this a few years ago and some of the issues have sorted themselves out, but not so many as one might think.

What is bioinformatics? A biologist's perspective.

Imagine this. You've been sequencing DNA for a few years now, perhaps ESTs, or something else, and storing files on your local network. Your system administrator makes backup files for you and all is well.

One day you learn about interesting results from assembling sequence data and decide to try it yourself.

Watch out! You are about to descend into bioinformatics hell.

Soon you learn that the assembly program has complicated requirements and demands that all files entering the system be given an incomprehensible name to comply with sequencing procedures from the last decade.

You beg someone to do something with the computer and rename your files. Meanwhile, the back-up files with the original names, that were referenced in experimental procedure and linked to experimental data, languish on the system, forgotten. A few months later, no one knows why those files are there. Your new files with their new names are backed up. More new files enter the system and quickly acquire two sets of names. More months pass, the server is loaded down with files, and no one knows why.

Your department head, frustrated with the slow network, hires an expert to analyze the system and determine if you need a Linux cluster. Oops, it turns out that many files contain the same information. Naturally, the older files are deleted. Now all information connecting the files to the original experiments is lost.

Your lab director says to quit fooling around and hires someone to move all of your data into a database. But, the next few weeks find you ranting at your computer. Why? You don't know how to use SQL and you have important research to do, dammit! The last thing you want to do is fight with your computer to get it to tell you something you don't already know. And, you start to wonder, what exactly is in those tables? And why tables? And how are you going to get your data back and do something useful with it?

Perhaps, you decide, it's time to hire a programmer.

The first person you interview is very enthusiastic. You ask about programming experience. Apparently, he can program in more languages than a UN interpreter can speak. And he's especially excited about some language called "open source" and some snake language. Confused already, you ask what he's done. It turns out that he's written games and designed something sticky or gooey (you think) and know lots about cold fusion. You're a little worried about using gooey stuff around your computer and puzzled by the remark about cold fusion (especially since it was a fraud), but you smile and nod, not wanting to betray your ignorance.

Time to switch to your domain.

Do you know anything about biology? you ask. The candidate smiles. Oh yes! He took biology in high school and read "Genome", too!

You hire him, pay him twice the salary of any of the post-docs, and have him start with something simple. You ask him to write a program to translate DNA into open reading frames. You're met with a blank stare. Is there a problem, you ask? What's an open reading frame? is the reply.

To quote Garrison Keillor, "Wouldn't this be a great time for a slice of rhubarb pie?"

Subject: Silly items

technorati tags: bioinformatics

Molecular resources for monarch biology

2005-09-09T12:39:00.000-07:00

One of the best places to get both sequence information and information on current research is the National Center for Biotechnology Information. The NCBI is part of the National Library of Medicine in the National Institutes of Health. One of the best known aspects of the NCBI is that they house GenBank, a collection of all the DNA and protein sequences that are publicly available. They also have PubMed, a database of scientific literature that's related to medical research.

To get sequence information for Monarch butterflies:

1. Go to the Taxonomy Browser at the NCBI

2. Search with the scientific name for monarchs: Danaus plexippus

This takes you to a page with the heading "Danaus plexiplus" and two subspecies. Click the Danaus plexippus link at the top of the list to get the taxonomy record.

There is a handy box in the upper right hand corner of the taxonomy record with useful links.

The links that are shown depend on the types of resources that are present in the NCBI databases. For monarch butterflies these links to records in the Nucleotide, Protein, Popset, PubMed Central, and Taxonomy databases. The numbers in the columns reflect the number of records. So, the nucleotide database has 52 sequences from monarch butterflies (as of this morning). The protein database has 72 total, for both of the subspecies.

You can also get the sequences straight from GenBank.

The other very handy links are Popset and PubMed Central. The PopSet reference for Danaus, is linked to a list of 12 different sets of sequences from population and evolutionary studies of butterflies. PopSet is a database with sets of sequences from evolutionary studies. If you look at the papers that are referenced in PopSet, they should include in the sequences for the primers that were used in the studies. The PopSet sequences are also great for making phylogenetic trees, but that subject will be a future post.

The PubMed Central link gives a list of several scientific literature citations for monarch butterflies. The cool thing about PubMed Central is that you can actually get the full text and read the entire paper, if you're so inclined. Scientific publishers are still experimenting with free, on-line access, so these may only be available for a limited time.

Subject: Web resources, Insects

technorati tags: biology, nature, butterflies