In this episode, I converse with Prof. James Fraser at the University of California, San Francisco. James was an undergraduate at McGill University, where he worked in the lab of Dr. Francois Fagotto on Xenopus developmental biology. As a graduate student, with Tom Alber at UC Berkeley, James established room-temperature X-ray data collection techniques and electron density sampling strategies to define protein conformational ensembles essential for catalysis. Prior to starting an independent position at UCSF, he was a visiting EMBO Short Term Fellow in the lab of Dan Tawfik at the Weizmann Institute of Science in Israel and developed expertise in directed evolution and high-throughput assays of enzymatic or binding activity. In January 2011, James started his independent career as a QB3 at UCSF Fellow affiliated with the Department of Cellular and Molecular Pharmacology. In January 2013, he was appointed as an Assistant Professor in the Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences (QB3) with promotion to Associate Professor in 2016, and Full Professor in 2020. James is also a Faculty Scientist in the Molecular Biophysics and Integrated Bioimaging Division of Lawrence Berkeley National Lab.

The long-term goals of James' research group is to understand how protein conformational ensembles are reshaped by perturbations, such as mutation and ligand binding, and to quantify how these perturbations impact protein function and organismal fitness. To accomplish these goals, they create new computational and biophysical approaches to study how proteins move between different conformational states. Additionally, the group uses two complementary approaches to study the relationship between protein conformational ensembles and function. To dissect consequences of mutations on organismal fitness, they use high-throughput systems biology and biophysical methods to analyze large sets of clinically or biophysically interesting mutations and to improve the ability to engineer new protein functions, they investigate changes to the conformational ensemble as new enzymatic and binding functions emerge from directed evolution studies. We indulge in a fascinating conversation on his enjoyable journey through science and life; foraying into academia from a family of non-academics; the thrill of methods development; the enormous influence of his brilliant mentors, friends, and collaborators; creating a more equitable, open, and just environment in science; and many more things!!