A Conversation with Betsey Dyer
Recent advances in mapping the human genome could radically change medical care and transform our understanding of our very identity. Research by Professor of Biology Betsey Dexter Dyer and Professor of Computer Science Mark LeBlanc place the pair in the thick of one of the most exciting, controversial and fastest growing areas of biology. In fact, they and two students authored findings recently published by the journal Genome Research. Dyer recently spoke with interviewer Nancy Bianchi Norton '78 about her scholarship, the team's work in the genomics field and how it relates to various genome projects, including the Human Genome Project.
Can you give us a basic lesson on genes and genomics?
Genes are sequence of DNA coding for proteins. Proteins are much of what we're made of and how we function. Genes are roughly equivalent to the "blueprint" of who we are. Our genomes are comprised of all our gene sequences plus all of the DNA sequences that are between the genes. Genomics is the analysis of genome structures and functions. Our particular approach is via a linguistic metaphor. We think of genes as words in a language that has not been completely deciphered. For example, if you're a writer for a living you don't simply hand your editor a dictionary and say, "here's my story" or "here are all the words that would be used in my story." There is much more to it. You have to put your words together with the proper syntax and grammar. What we're calling syntax and grammar in our model is the regulation of genes using the genes together in a logical way to form complex, multicellular organisms. There are tens of thousands of human genes. But what a lot of people don't realize is that only about 10 percent of the total human genome - all of the DNA - is made up of actual genes. Our question is: "What about the other 90 percent? How do we analyze that?"
So what is that other 90 percent?
It's called the intergenic sequence and it's the most difficult part of the genome to annotate. That's what we're trying to do here -with success - in our tiny genomics lab here at Wheaton.
Why do you want to annotate the intergenic material?
Think of a stage of human growth and development - the fertilization of an egg, for example. A couple of weeks after conception the fetus starts forming a nervous system; if it doesn't, serious problems will follow. The intergenic sequence contains information that somehow says "Yes, we're going to use this gene this time in this particular place," or "We'll save this one to use later or in a different place." It's a subtle thing. It's timing, it's spacing, using one gene now then perhaps shutting it down, then using it again later, then shutting it off again. The intergenic sequences are the information that, for example, instruct eyes to develop in the front of the head instead of all over the body. What we're trying to get at through our research is a genomic approach to how to get the genetic vocabulary organized, how to put the correct structures together. So that you end up with a coherent organism and not just a blob.
How did you get started looking into this?
I've always been interested in how genes are regulated, but it was something I didn't think I would be able to get a handle on because it's just too big of a project. One day Mark LeBlanc (professor of computer science) asked me if I thought there were any large problems in biology that might benefit from a computer analysis. I didn't really believe this was something that could be done - it's just too big. But I casually brought the project up and thought maybe we could begin to try to analyze some of these intergenic sequences. The answer turned out to be "Okay. Let's do it." We're doing it in kind of a naive way. We don't have to answer to the CEO of a big biotechnology company, in which case we probably wouldn't have had the luxury of being able to play around with this. We both felt really brave about tackling a really huge problem and enjoying all the steps, even the ones that go slowly.
And some of your students are actually part of the research team?
Mark and I started this work by making up a class project between my cell evolution class and his algorithms class. Two students, Nate Buggia '01 and Glen Aspelagh '00 worked with us for a long time on the project. They turned out to be wonderful programmers and we just published a paper with them that we consider an accomplishment. Two other students, Trevor Agnitti and Melissa Kimball, spent the summer working on the project as Mars Fellows, and we'll be busy recruiting others in the fall. In addition to our research, we've developed our own genomics website (http://genomics.wheatonma.edu). It includes an annotated catalog of inverted repeats, which are like palindromes, and it includes some of our ongoing projects: our "favorite gene project" and our motif dictionary - something our students have been working on all summer.
This sounds like you're settling in for the long haul?
That's one of the things I like about this project. Not only do I like its aesthetics and the way we can get students involved in a really meaningful way, I also like the size of the problem. When I first suggested it to Mark I was almost laughing to myself because it was so huge and seemingly impossible. But we're doing it, and it's great!
Are other researchers working on the same thing?
Many. This is considered a big problem in science; a really big problem. Many people have done lots and lots of work on gene regulation in regular biochemistry and molecular biology labs for decades. What's new about genomics is that for the first time we have sequences for whole genomes - a relatively new thing - and it means we can tackle the problem from a whole new angle. Rather than working on one gene or a few genes at a time, we can back away from it now and say "Here are millions of base pairs, let's write a great big computer program to analyze them as a whole." We couldn't do that then.
Then just how old is this field?
Just as soon as people started to generate DNA sequence they started to try and analyze it, so I guess you could say it's been around since the mid to late 1970s. On the other hand, it really hasn't been up and running as a Major field, except in the last four or five years or so. Not only is it new science, it's a new approach. It's the difference between looking at a few genes at a time to stepping back and cataloguing all the genes and other sequences at once.
So how does what your doing relate to the human genome project, which made headlines around the world this spring?
We started in December 1998 on the first complex organism to be sequenced: Caenorhabditis - a worm. Because the community of people who have been working on it for such a long time are so cooperative with each other the data was available immediately and we could download the sequence. The human genome, in contrast, is quite commercial. At the moment it is not being presented in as user-friendly a way as Caenorhabditis's, no matter what the popular press might tell you. We're not ready to go in confidently and spend a lot of research time on it yet. When the human sequence data has been stabilized and is more available, we'll be able to apply a lot of what we've already done.
Are you saying the news media over-hyped the progress that's been made in mapping the human genome?
It's certainly a milestone, but the announcement had more economic than scientific significance. Celera is calling the mapping of the human genome complete, but there is still an awful lot of work to be done to check the information and make it useable. That will take many people many years.
I understand that you're involved in another research project, but a rather unusual one.
Where else but at a college like Wheaton can an English professor and a biology professor have lunch together often enough so that they can become friends and so that they can collaborate on research? I got to know (Assistant Professor of English) Mike Drout, and I'm interested in the sort of things he is - Anglo-Saxon literature and language, for instance. He half-jokingly asked one day what might happen if we were to concoct this medicine that seems to have been applied to styes in people's eyes in the Middle Ages and find out whether it works on the kind of bacteria that causes styes. I told him that was fairly easy to visualize from a scientific standpoint, and he held me to that!
Is that happening now?
Well, you can smell it because it's in the next room and it has garlic, and some onions, and some wine, among other things. We're putting bacteria on a Petrie dish - we're not actually using a human subject to test it! The whole thing is making a kind of smelly concoction that I'm sure will kill some bacteria.
You have a book that will soon be published. What's it about?
It's called "A Field Guide to Bacteria" and it contains descriptions of all of the major groups of bacteria using their macroscopic field marks. Cornell University Press will be the publisher. I hope it will be out in 2001.
On your web page you list "thinking" as one of your interests. What do you like to think about?
I do an awful lot of thinking about science and the research I'm doing. It's probably one reason why I can be a little un-social, but it's a good way for me to come up with ideas. I like visualizing things. And if I have something to do - say, a lecture - I'll actually visualize the entire lecture, or if I am writing a paragraph of a paper.
What else do you do in your spare time?
Well, as a working mom outside of the home I like to involve my kids in what I do. So they're at Wheaton a lot, especially during the summer. This summer we had a genetics club. We meet about once a week and the project has been to construct a DNA model. I also like to dance - tap and ballet. Ballet is my favorite. I read a lot, too.
I also know you're a termite fan.
I love bugs and have since I was a little kid. In fact, I always thought I'd be an entomologist before I even knew there was such a profession. It was something that came into my mind when I was about five years old, so it was before I knew there was even a possibility. And I was amazed when I was about 13 to find out that there really was a field called entomology. It was a huge revelation!
In a way I AM working with insects. It's a kind of promise I've always kept to myself. Who else has a box of termites on their desk? In graduate school for a short time, I was in an entomology program - finally! [^] but then I drifted into the path of my Ph.D. advisor who happened to be working with termites [^] but with a focus on the microorganisms inside them.
You have a colony of termites on your desk?
Oh, (holding aloft a box of South American termites) termites are a beautiful system in and of themselves! I like keeping them around and I still do some research on them or at least on their intestinal microbes.
What do you feed them?
Wood! And paper towels. Any paper product keeps them happy.