Connie Jeffery, associate professor in the Department of Biological Sciences at the University of Illinois at Chicago, loved math and science as a kid, but enjoyed all of her classes in school — except gym. She read books from the library about science projects, and even built a crystal radio when she was about eight. “We had toys like a chemistry kit and a microscope, and Mom and Dad gave us a lot of freedom to experiment with (messy) things like mixing vinegar and baking soda in test tubes or catching bugs in the backyard and putting them on microscope slides,” she says. Her mother was a dental hygienist who focused on being a homemaker after getting married, and her father owned an electronics shop until she was 12, and then worked as a technical support specialist. “He could fix anything electronic,” she says. “One summer when I was about 12, he put together a computer and I taught myself to program it in Basic.”
As she got older she found herself drawn towards science and math, and decided to major in science in college. “Around the time I was in high school the idea of gene cloning was entering the mainstream news, and I saw it described in magazines like Time and Discover when I was working in the library at my high school,” she shares. “It seemed these were some breakthroughs that would open up incredible possibilities in science. I read that the research was being done at a place called MIT [Massachusetts Institute of Technology], so I decided I had to go there for college.”
She did just that, earning her bachelor of science degree from MIT in 1987. “During my undergraduate years, two professors generously gave me the great opportunity to do projects in their labs: Bill Orme-Johnson in chemistry and Dave Raulet in immunology. But I was unsatisfied with working at the cellular level, which at that time seemed like a black box with, for example, some cell lines behaving one way and others behaving another after the same treatment, and not really knowing what was going on inside them.”
Jeffery then began graduate studies at University of California, Berkeley. She attended a talk in her first year by Dan Koshland, in which he described work on the aspartate receptor. “It was fascinating that we could know which molecule transferred information across the cell membrane and how parts of it actually worked,” she says. She joined Koshland’s lab. “Dozens of mutant proteins later — and an agonizing six months trying to get DNA sequencing to work reproducibly in which I almost quit science altogether — I still didn’t feel that I knew much about how the aspartate receptor worked,” she shares. “Then, members of our lab collaborated with a crystallography lab to get the X-ray crystal structure of the extracellular ligand binding domain. The difference between knowing the amino acid sequence and having a three-dimensional structure was immense. Still, I decided that to really understand how proteins worked, I needed to learn how to solve their structures myself.”
With that goal, she undertook a postdoc with Greg Petsko and Dagmar Ringe at Brandeis University. “While there, I worked on several projects and proteins, but one that stood out was phosphoglucose isomerase. This was the last of the glycolytic enzymes to have its structure solved, so there were about a hundred years’ worth of papers about it in the literature. As we searched for all the papers about its catalytic mechanism, we found a few papers that seemed to be describing completely different proteins — autocrine motility factor, neuroleukin, differentiation and maturation mediator — extracellular cytokines, but the proteins that did these other functions were identical to phosphoglucose isomerase,” Jeffery explains. “This seemed very strange because at that time the general model was that a gene evolved to encode a protein with one function. It was thought that a protein couldn’t have two different functions because there wasn’t a model for how evolution could select for the two different functions simultaneously. But I’d heard of a few other examples, so I wrote to the editors of Trends in Biochemical Sciences and asked if I could write a review article about multifunctional proteins. After they said yes, I scoured the literature for more examples and also made up the name “moonlighting proteins.” The article was published, the name stuck, and something I thought of as an interesting curiosity became a big part of my lab’s research program because these proteins gave us a lot to think about: how a structure can accommodate multiple functional sites, mechanisms for switching function, how they evolved two functions, how we might use that information to design new proteins, how can we predict a protein’s function(s), etc.”
Following her postdoc, she took a position in the Department of Biological Sciences at the University of Illinois at Chicago. In addition to their work on moonlighting proteins, her lab has collaborations with other labs working on cancer and tuberculosis, and a project on how genetic mutations affect protein structure and function.
She faced major challenges as she was setting up her lab. “I was assigned far too many committees and service and other extra requirements that filled up a lot of my time but didn’t really help anyone or do anything productive [She later learned this is a challenge faced especially by young women faculty]. At first, I lost a lot of valuable time to these things, but over the years I developed strategies to protect time for research and writing,” she says. “For solving this and other challenges related to running a lab I read articles and books like Making the Right Moves: A Practical Guide to Scientific Management for Postdocs and New Faculty (from the Burroughs Wellcome Fund and Howard Hughes Medical Institute) and At the Helm: Leading Your Laboratory by Kathy Barker, talked to colleagues in other departments, and attended workshops.
Jeffery was also painfully shy, and had a major fear of public speaking. She knew she would have to conquer it, so she went to workshops on giving presentations, read articles on the subject, and attended relevant webinars. “I had to force myself to give talks and get over the phobia. Teaching biochemistry to hundreds of undergraduates also improved my ability to give presentations and think on my feet,” she shares. “Now I still get nervous but also excited to share science and my research with my students and colleagues.”
Now she is working on ways to increase her lab size, because of the huge number of research ideas she hopes to follow. “In addition to completing a lot more research, I’d like to use my knowledge and experiences, both good and bad, to help level the playing field for women and minorities,” she says. Jeffery currently serves on the Biophysical Society’s Committee for Professional Opportunities for Women and volunteers for the 1000 Girls, 1000 Futures and STEM Scholars programs through the New York Academy of Sciences.
Advising young biophysicists, she says, “Find out what you are really interested in and go after it. If you come up with an idea, be bold enough to follow it. Also, don’t let anyone or anything inhibit your education or your career because you are a different color or gender or sex or religion or nationality or you come from a poor family or have a disability. Even though there might be some people who get in your way, there are far more people who want to help you succeed.”