Biophysics, Structural Biology
Massachusetts Institute of Technology
Dr. Drennan is also a professor of chemistry and biology and an HHMI professor at the Massachusetts Institute of Technology.
The Drennan laboratory seeks to understand how nature harnesses and redirects the reactivity of enzyme metallocenters to perform challenging reactions. By combining x-ray crystallography with other biophysical methods, their goal is to "visualize" molecular processes by obtaining snapshots of enzymes in action.
Catherine Drennan has come a long way from the Scattergood Friends School, a Quaker boarding school and working hog farm in Iowa where she taught biology, chemistry, physics, and drama after college. There, each of her biology students was assigned a pregnant hog. The final exam: help bring a litter of piglets into the world.
Today, Drennan is a professor of chemistry and biology at the Massachusetts Institute of Technology (MIT), where she specializes in creating three-dimensional pictures of proteins that harbor metals such as nickel and iron and then figuring out how those proteins work. Just as she delighted in opening the eyes of high school students to biology through hog reproduction, she is thrilled to watch her MIT students make never before seen pictures of protein molecules.
In choosing molecules to study, Drennan zeroes in on proteins vital to biological problems, such as enzymes important for understanding how nature removes greenhouse gases from the environment. Her colleagues say Drennan is guided in part by a keen ability to recognize the problems where new information about the structure of proteins will have the biggest impact on understanding.
Once she identifies her target, she approaches it fearlessly. "I'm not a big risk taker in my personal life. I'm an enormous risk taker in my professional life," she says. "It's hard for me to let a problem go. My group has taken on projects that other groups have abandoned."
In particular, Drennan revels in sorting out the architecture and function of metalloproteinsthose proteins whose structure contains one or more metal ions. Blending metal with amino acids, Drennan notes, is nature's way of managing difficult but critical reactions, including things such as photosynthesis. "The most fundamental, simple reactions require the most complex metalloproteins," she explains. "Anything that is really hard often has a metal-containing protein. And the hard ones are really the fun ones, where there is the most to learn."
To create the molecular pictures, Drennan and the members of her lab use x-ray crystallography, a technique in which protein crystals are bombarded with x-ray beams. As the x-rays pass through and bounce off atoms in the crystal, they produce a diffraction pattern that researchers can use to determine the molecule's three-dimensional shape. Drennan's lab is not satisfied to create a single picture of an enzyme they want to understand. Instead, thanks to advances in the technologies underlying x-ray crystallography, they capture multiple snapshots of molecules as they march through reactions. By blending the images of a reaction in progress with molecular biology, biochemistry, and spectroscopy, her group can map in precise detail how a protein catalyst works. "I've become fascinated by these reactions. I want to know how they happen. I want to dissect them down."
Drennan finds her own career trajectory just as surprising. As a doctoral student at the University of Michigan, she found the thought of a tenure-track job at a place like MIT was a distant one until JoAnne Stubbe, an eminent biochemist at MIT, suggested it to her. "My initial response was, 'Is she talking to me?' I hadn't thought of being at an MIT-type place. It wasn't on the list. But when someone else put it on the list, I thought, why not?"
At MIT, Drennan has excelled at both research and teaching, harkening back to her work with high school students at Scattergood. In 2006, she was chosen as one of 20 HHMI professors, a group of scientists from research universities who are bringing the creativity they have shown in the lab to the undergraduate classroom. As an HHMI professor, Drennan has redesigned introductory chemistry classes to highlight their relevance to biology. She is the first HHMI professor to be named an HHMI investigator.
"My love for teaching people and watching my students grow gives me great pride and joy," Drennan says. "To be a good researcher, you have to be a good teacher. They really go hand-in-hand. If a student comes up with an idea that I didn't think of, that's an incredible joy to me."