麻豆淫院

Growing up with a father who taught at Cornell University, and surrounded by friends whose parents were also on Cornell faculty, Amy Keating had little doubt that she would follow the same path.

鈥淚t didn鈥檛 seem at all unusual that [academia] would be a career path that you might take,鈥� Keating says. 鈥淚 was pretty much on that track most of my life.鈥�

The only question: What field to pursue? Keating鈥檚 academic career has taken a winding path through math, physics and chemistry to her eventual appointment in MIT鈥檚 Department of Biology, where she recently earned tenure. Much of her research focuses on computer modeling of the interactions between proteins. Though her work may have potential applications in drug development, she鈥檚 driven by sheer interest in understanding the physical phenomena involved.

鈥淚 bounced around a lot of scientific areas and they didn鈥檛 all grab me like this one does. It鈥檚 a geeky thing 鈥� I just like to know how these protein interactions work,鈥� she says.

From physics to chemistry

In high school, Keating was drawn to physics and math; she ended up majoring in physics at Harvard University, where she also spent a lot of time rowing. She worked in physics labs during the summers, but most of them didn鈥檛 excite her. During this time, she had 鈥渁 physics student鈥檚 disdain for biology,鈥� she recalls. 鈥淚 was almost aggressively anti-biology.鈥�

After college, she planned to enter a physics PhD program at Cornell, but 鈥渟ort of panicked at the last minute and decided it wasn鈥檛 really what I wanted to do,鈥� she says.

Her then-boyfriend (now her husband) was a chemistry major at Harvard who got her interested in physical organic chemistry 鈥� the study of how molecules鈥� chemical structures influence their reactivity. 鈥淚t had a lot of the physical principles that I was interested in but also was more intuitive to me than physics,鈥� Keating says. She stayed at Harvard for another year, taking chemistry classes and working in an atomic molecular physics lab.

She then went to graduate school in chemistry at the University of California at Los Angeles, where she did computational studies of the reaction mechanics of organic molecules known as carbenes. After finishing her PhD, she faced a limited job market. 鈥溌槎挂�院ical organic chemistry is not a huge field, so I had to look at where it could be applied,鈥� Keating says. 鈥淏asically it boils down to, you can do biological applications or you can do materials-science applications.鈥�

She found both interesting, but ended up at MIT鈥檚 Whitehead Institute for Biomedical Research as a postdoc in Peter Kim鈥檚 lab, collaborating closely with Bruce Tidor, a professor of biological engineering and computer science and electrical engineering. Kim and Tidor worked on protein biochemistry with a particular interest in coil-coil protein interactions 鈥� an association that occurs between pairs of proteins shaped like helices. Keating鈥檚 job was to tweak the sequences of the proteins involved and develop computer models to predict how those changes would alter the proteins鈥� interactions.

Learning by immersion

Nearly all cell functions rely on precise interactions between proteins, determined by the structure of the proteins involved. Small changes in structure or amino-acid sequence can have a big effect on how those proteins connect.

Though her training in physical organic chemistry helped her understand much of the biochemistry involved in those interactions, she had very little background in biology and found herself learning the field by immersion. 鈥淚 didn鈥檛 know any of the amino acids. I knew nothing, in terms of formal training in biochemistry, and certainly not biology,鈥� she says. 鈥淚 suppose I probably read some books, but I think I mostly just asked the people who were sitting around me to explain things.鈥�

After four years at the Whitehead Institute, Keating started looking for faculty jobs in biology, chemistry and biochemistry. At the last minute, she applied for an opening created in MIT鈥檚 Department of Biology after Kim decided to leave, and was hired. 鈥淚 don鈥檛 think I ever would have called myself a biologist before that. I still don鈥檛,鈥� she laughs.

Since starting her own lab, Keating has tried to replicate the diverse range of interests and skills that she found in Kim鈥檚 lab. 鈥淚 really like the team-based aspect of running a research group,鈥� she says. 鈥淲e鈥檙e working on all kinds of projects that I never would have dreamt up in isolation.鈥�

鈥楳ix and match鈥�

Keating鈥檚 group now focuses on computational modeling of two different types of protein interactions. The first is a coil-coil interaction within a family of proteins called bZIP transcription factors, which control the expression of genes. Each bZIP transcription factor consists of two helical proteins bound together; there are 53 possible versions of the helices.

鈥淚t鈥檚 a sort of mix-and-match game, where we can try to understand, among the different pairs you can form with 53 proteins, which ones are preferred and which ones are not,鈥� Keating says. The lab is also studying how the pairings differ in their ability to bind DNA.

Another target is the Bcl2 family of proteins, which also come in pairs 鈥� one coiled protein bound to a more globular protein. These proteins are important for regulating programmed cell suicide. Cancer cells often have too much Bcl2, which appears to help them stay alive, so drug companies are now working on drugs that inhibit the protein.

Though her work may eventually help with that kind of drug development, Keating鈥檚 team is focused on fundamental questions of how proteins work, and how those workings can be modeled.

鈥淲e鈥檙e not motivated by any one application, but just by the fact that scientists鈥� current ability to predict or design protein-protein interactions is poor,鈥� Keating says. 鈥淭he future of biologic drugs, synthetic biology, and diagnostic and detection technologies requires that we do better.鈥�

This story is republished courtesy of MIT News (), a popular site that covers news about MIT research, innovation and teaching.