A fundamental obstacle to understanding the rules of Life, is the lack of a predictive, molecular understanding of the mechanisms by which the genome encodes the function of a protein. This project will provide biophysical information on how the amino acid sequence and the environment tune a protein's energy landscape, the mapping between protein structure or conformation and thermodynamic properties which govern its stability. This connection between amino acid sequence, environment and energy landscape is imperative for the ability to design proteins with targeted behaviors such as function, mechanical properties, and lifetime. In addition, the PI will develop a program to provide broad career exposure, exploration and experience to graduate students and postdocs in the life sciences at UC Berkeley. A novel Professionals in Residence (PIR) program will be instituted, where professionals from diverse fields (Industry and Entrepreneurship, Education and Outreach, Policy and Communication, Academic and Research Institutes) will spend several days a year at UC Berkeley interacting with both trainees and faculty - exposing them to successful professionals from a variety of career paths.
The scientific objective of this research is to investigate the protein-folding problem using single molecule mechanical studies and hydrogen exchange techniques. The results from this work will further our understanding of protein folding, the mechanism by which the amino acid sequence directs the energy landscape of a protein (the structures, energies, and rates of interconversion of all of the accessible conformations), a major challenge for modern molecular biology. Without a better understanding of how these features are encoded in a protein sequence, the expanding sequence databases continue to conceal the answers to many important questions. The results of the single-molecule protein folding studies will yield observables that can be used directly in theoretical studies of protein folding and the experiments will be carried out in an iterative collaboration with theoreticians in the field. Mechanical stress plays a ubiquitous role in protein function and biology, and therefore, in addition to providing needed insight into the protein-folding problem, this work will also provide much needed information about the mechanical stability of proteins.
This project is jointly funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences and the Physics of Living Systems Program in the Division of Physics.
