This week we shine a spotlight on alumna MIT biologist and president of The Protein Society, Professor Amy Keating (PhD ’98 Houk/García-Garibay groups).
A Professor of Biology and Biological Engineering at the Massachusetts Institute of Technology (MIT), Keating’s research involves working to understand how protein sequences and structures encode interaction specificity. Her lab uses computational and experimental methods to measure protein interactions in high throughput, predict new interactions, and design proteins and peptides with novel interaction properties.
Keating is President of the Protein Society (2019-2021), a global organization that promotes a wide range of protein science by running the journal Protein Science, fostering a community that welcomes protein scientists from all backgrounds and career stages, and running an annual international symposium.
After graduating from Harvard University with a degree in physics in 1992, Keating developed an interest in organic chemistry and reaction mechanisms and joined UCLA’s organic chemistry program working with Professors Ken Houk and Miguel García-Garibay.
“I went to UCLA specifically to work with Ken,” Keating said. “He sold me on the beauty of using quantum mechanics to predict and understand exquisite details of chemical reaction mechanisms. He also sold me on sushi, which I had never tried before visiting UCLA as a prospective student. I was (and remain) very intimidated by how smart Ken is, and by his amazing chemical intuition, which benefited me a lot in graduate school. I got great training and advice not only from Ken but also from many talented postdocs and older students in the Houk group.”
In her graduate work she applied computational and experimental methods in physical organic chemistry to the study of carbene reaction mechanisms. Her thesis involved applying molecular mechanics and quantum mechanics to study carbene rearrangements in gas, liquid and crystalline phases.
“I had a really fun time working on carbenes as a graduate student and it provided me with some nice collaborative opportunities,” Keating explained. “When I realized that then-assistant professor Miguel García-Garibay had complementary interests and perspectives on carbenes to what I was studying with Ken, that led to a terrific co-mentoring relationship that broadened my experience and provided me with access to two supportive and caring advisors.”
After receiving her Ph.D. in organic chemistry from UCLA in 1998, Keating worked on protein interactions as a Helen Hay Whitney postdoctoral fellow in the Whitehead Institute with Professor Peter Kim and the MIT Chemistry Department with Professor Bruce Tidor, where she was introduced to protein biochemistry. She joined the MIT faculty in 2002.
Keating’s husband, Tom Keating, also received his Ph.D. in organic chemistry from UCLA in 1998, working with former UCLA chemistry professor Dr. Robert Armstrong. He has had a very successful career in the pharmaceutical industry.
Keating was recently profiled on the MIT Computational and Systems Biology website:
Human-human and protein-protein interactions by Jacquie Carota (November 2019) – Photos courtesy of Professor Amy Keating.
A change in fields and a two-body problem ultimately led Biology and [Biological Engineering] Professor Amy Keating to MIT to study coiled-coils and other protein interactions.
About 330 miles west of Cambridge lies the small academic town of Ithaca, New York: the location of Cornell University and the hometown of Professor Amy Keating. Surrounded by academics (her father is a professor of computer science at Cornell), Keating was eager to continue her education after high school—just not in Ithaca.
“I could have stayed at Cornell, which is obviously an extremely good school in my hometown, but my family and I agreed that it was important that I go away,” recounts Keating. The scholar/athlete set her sights on Harvard University based on the excellent rowing team and outstanding academics. Physics particularly appealed to her, because it involved using math to explain mechanical and electrical phenomena, and she chose this as her major. She likes to tell people that she also “attempted pure math but failed miserably.” Keating admits that she was not very good at the abstract subject material, and tackling it side-by-side with math whizzes was a harsh awakening after performing well throughout high school. She switched to studying applied math, which was easier for her to manage and also more useful for a physics major.
With an intense rowing schedule, Keating often found herself working late into the night, struggling to solve problems alone. It took a year or two and a serious injury for her to realize that that most of the physics majors were working together in the library many afternoons while she was on the river. “That was very eye-opening. Now I’m a strong advocate of students teaching each other and learning from each other,” explains Keating.
Graduate study gridlock
As she approached the end of her senior year, she had no doubt that she would pursue a PhD, but she did face a crisis about what to study. Initially, she thought she would go to graduate school for physics and applied to and visited many schools. However, she was troubled by the fact that she had tried out a number of areas of physics but never found one that truly captured her interest. In addition to this, Keating began dating a young man, now her husband, who was majoring in chemistry and not set to graduate for another year. “I learned a lot of organic chemistry from him and got very interested in the subject.”
With the decision made to stay in Cambridge for an additional year, she picked up part time work at a Harvard student residence hall cooking, baking, and cleaning in exchange for room and board. Keating also took a few chemistry courses for credit, coached adult rowing, and spent the rest of her time working in the lab of Harvard Physics Professor Mara Prentiss. By the end of that year, she had developed a keen interest in the field of computational chemistry. Having faced difficult decisions about her own post-college plans, she has “a lot of empathy for students who are twenty-one and trying to decide what they want to do in the world.”
Keating and her future husband applied to the same chemistry PhD program at UCLA, where they were both admitted and joined separate labs. She looks back at the interview weekend at UCLA and remembers one faculty interviewer [Professor Yves Rubin] who pointed out the lack of chemistry in her background. “We were talking about cooking, and I told him I like to cook and had been cooking for a job. He said ‘if you can cook, you can do chemistry’, and there is some truth to that, of course.” Keating acknowledges that the first few months of graduate school were traumatic. “I had exactly two undergrad chemistry classes under my belt. I didn’t really know much chemistry and then I was thrown into this PhD program with chemistry majors. And I was taking graduate level courses with my husband, who is a brilliant chemist. But I caught up and managed to learn a lot in a short time.”
Graduate life smoothed out when Keating joined the lab of Ken Houk, a leader in computational physical organic chemistry. Later in her doctoral studies, she added co-advisor Miguel Garcia-Garibay, an expert in experimental photochemistry. Having the two advisors worked out well and led to several joint publications over Keating’s graduate school career. After her husband’s advisor left UCLA for a company, the couple “had to decide what to do. So, we decided we should graduate quickly.” Now married, Keating and her husband earned their PhDs in under five years, but they would continue to be challenged by the “two-body problem” as they formulated a plan for after graduation.
Further afield
The couple knew they both wanted to find postdoc positions, so they looked in cities like San Diego, San Francisco, and Boston, where positions were abundant. Of that time, Keating says: “I was thinking about different problems or fields where my background might apply. I was reading a lot, just to find out what was out there.” This also marks the first time that she started thinking about problems in biology. “I was actually interested in two areas: material science, and biochemistry, both of which are exciting and rapidly growing areas where chemical principles are centrally important.” Keating’s hard work landed her a position back in Cambridge, where she was again co-advised, this time by former MIT Biology Professor Peter Kim at the Whitehead Institute and MIT Professor of Chemistry Bruce Tidor (who was later the founding director of the CSB PhD Program).
The postdoc transition was another time in Keating’s life that she good-naturedly describes as “traumatic,” as she once again had to work to understand all-new vocabulary and experimental methods. Her postdoc provided Keating with her first exposure to large molecules; it was also when she first started working on protein interactions, which would become the crux of her future research. It was in the Kim Lab that she was introduced to coiled-coil proteins. With her background in physics and chemistry, the simplified repeating interactions in these molecules appealed to her. A principle the Keating Lab continues to follow to this day is that they try not to study the most complicated interactions in biology, but rather simpler interactions that they seek to understand in fine detail.
More two-body problems
After four years, Keating hit the academic job market, but she wasn’t sure if she would be accepted as a biochemist because of her change in fields as a postdoc . Her concerns were short-lived as she ended up with a number of exciting offers, including one from MIT. Keating’s husband decided he would go into industry in Boston and with this decision she accepted MIT’s offer to join the Biology faculty in 2002. Later, she added a joint appointment in Biological Engineering.
Keating offers advice to students who are dealing with the two-body problem as she once did.“I think something that helped me and my husband is that we stayed in sync. So, we never had one person make a decision without knowing how that would impact the options of the other person. Of course, that’s not possible for everybody. But that did make our trajectory easier. We would collect our options, put them on the table, look for overlap, and then try to figure out what decision would work best for both of us. And we were very fortunate that we had good options. People have to be flexible to make this work out.” She also recommends looking in cities where there is a high density of opportunities.
The general interest of the Keating lab is in protein-protein interactions, how they work in nature, and how they can be re-engineered using computational and experimental methods. Her group studies proteins that regulate critical processes but are also relatively simple. For example, a system the Keating lab is attracted to is the Bcl-2 family of proteins that control cell death. They have developed a variety of methods that can be used to reprogram the interaction between proteins, and applying these methods to Bcl-2 proteins has generated short peptide molecules that inhibit processes that keep cancer cells alive. Recently the lab has been investigating other types of interactions in cells that are structurally different from the Bcl-2 family. Switching protein families challenges them to develop new methods and allows them to continue to change and evolve their research.
Students and postdocs from the Keating lab have gone on a wide variety of jobs where they study proteins and their interactions in both academia and industry. Keating is happy that young scientists today have so many options. She reflects: “When I was finishing my postdoc, the range of jobs in industry was nothing like it is today. It has been fun to watch my trainees apply their skills to antibody engineering, cancer biology, immuno-oncology and even to start their own companies.” She marvels at how many paths are open to young biologists and likes to tell them that they can’t possibly forsee where they will end up, given the myriad exciting possibilities. Certainly, as a young rower and physics student at Harvard, she had no idea she would end up as a Professor of Biology at MIT.
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Penny Jennings, UCLA Department of Chemistry & Biochemistry, penny@chem.ucla.edu.
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