Alex Holehouse, PhD, an assistant professor of biochemistry and molecular biophysics at Washington University School of Medicine in St. Louis, has received a Faculty Early Career Development (CAREER) Program award from the National Science Foundation (NSF).
The five-year, $1.3 million award will support Holehouse’s research into intrinsically disordered proteins. These proteins play important roles in biology but are difficult to study because they have no fixed 3D shape. The dysregulation of these regions has been implicated in a variety of diseases.
This CAREER award will focus on understanding evolutionary principles associated with disordered regions. Holehouse plans to use accelerated artificial evolution and new computational methods to learn how evolutionary pressures can influence changes in these regions. Holehouse explained that the primary goal of his CAREER proposal is to develop the tools needed to understand how evolution shapes disordered protein function and understand why some mutations are tolerated while others are not. In the long term, a more robust understanding of how mutations in disordered regions impact their function has implications for understanding human disease, as well as designing synthetic disordered regions that could be used for biotechnological applications.