Biochemist Dr. Susan Taylor, a Professor of Chemistry, Biochemistry, and Pharmacology at the University of California, San Diego (UCSD) is best known for solving the first crystal structure of a protein kinase (PKA), which has become the “prototype” for these diverse cellular regulators. But, to her colleagues, she is known for much more – a high-energy passion for learning and teaching and a sincere dedication to mentoring a diverse “next generation” of scientists.
Taylor was born in Racine, Wisconsin. She studied chemistry at the University of Wisconsin, then went on to receive a PhD in physiological chemistry from Johns Hopkins University (1968), followed by postdoctoral work at the Medical Research Council’s Laboratory of Molecular Biology (MRC LMB) and UCSD, where she quickly joined the faculty, becoming a full professor in 1985.
She didn’t always know she wanted to be a biochemist. She fell in love with chemistry as a freshman at the University of Wisconsin and, as is so often the case, it was thanks to a great teacher who took the time to work closely with the students. She credits her professor Dr. Charles Sorum with convincing her to major in chemistry, but at that time she had her sights set on medical school.
It wasn’t until her postdoctoral fellowship at the MRC, where she was introduced to working with proteins, that she decided a PhD, not an MD, was the path she wanted to pursue. So, when she returned to the US, she took the initiative to earn herself a postdoctoral position at UCSD. And, from then on, it was protein biochemistry for the win!
And “win” she has – Taylor has won numerous awards and honors including election to the Institute of Medicine (1996) and National Academy of Sciences (1996). She was a Howard Hughes Medical Institute (HHMI) investigator from 1997 to 2014, served as an editor of the Journal of Biological Chemistry (JBC) from 1985 to 1990, and served as president of the American Society for Biochemistry and Molecular Biology (ASBMB) in 1995.
Despite, or perhaps because of, her successes, she’s never forgotten the impact that Dr. Sorum had on her life and she has successfully emulated his thoughtful, patient, and compassionate teaching style. She loves teaching to all who want to learn – undergraduate students, graduate students, and medical students. She especially liked teaching a biochemistry and metabolism course for undergrads and med students because she “could include how everything was regulated.” And regulation’s kinda her jam!
Taylor studies some of the cell’s master regulators – kinases – which add negatively-charged phosphate groups to molecules to get them to change their activity to do things like relay messages throughout the cell.
In 1991, Taylor, put together and led an interdisciplinary team to answer the question – what does a kinase look like in 3D? In collaboration with Janusz M. Sowadski (a crystallographer), Lynn Tenn Eyck (a computational crystallographer), and Nguyen Xuong (who developed some of the data-collection hardware), Taylor led two of her graduate students, Daniel Knighton and Jianhu Zheng, on a successful quest to find out.
The team became the first to figure out what a protein kinase looks like in 3D by solving its crystal structure (x-ray crystallography is a technique that beams x-rays at crystals of things like proteins, lets them rays bounce off the protein’s atoms and onto a detector, then works backwards to find the atoms’ positions based on the hit points).
Crystallography had been used to study proteins before, but, before Taylor, no one had been successful in using it to solve a protein kinase structure. The kinase she chose, Protein kinase A (aka cyclic-AMP-dependent protein kinase), is a really important kinase, but the structure had implications far beyond “just” PKA – it turns out that the core parts of all sorts of kinases are really similar, so Taylor’s PKA structure has become a “prototype” for all protein kinases.
Solving the structure wasn’t the “end” of the quest to understand PKA. Taylor didn’t stop working on PKA once she solved the “structure part.” Instead, she has continued to pursue questions about how that structure affects the protein’s activity.
It’s important that kinases be carefully regulated. If they “go rogue” diseases like cancer can develop – which has made kinases a potential target for cancer treatments. You might have heard of the anticancer drug Gleevec – it targets a mutated kinase responsible for some forms of cancer. Work on Gleevec was pioneered in large part by Dr. Brian Druker, whom Dr. Taylor actually taught while he was in med school.
Kinases are tricky to target, especially because those same similarities between kinases that make PKA a useful prototype also mean it’s hard to target just one of them. So it’s important that scientists understand as much about them and their regulation as possible.
Taylor has therefore solved structures of regulatory subunits – alone and attached to PKA. The attached versions were particularly informative because they showed how the regulatory proteins change the catalytic part’s shape and thus its activity. In addition to getting “static images” of the protein with crystallography, she uses a variety of other techniques to study how the protein moves.