2237A Chemistry Building (Mathews Wing)
1101 University Ave
Madison, WI 53706
B.S., Chemistry, California Institute of Technology
Ph.D., Chemistry, Yale University
Postdoctoral, Harvard University/The Broad Institute
- NIH Bibliography
Protein engineering, directed evolution, and protein folding
Protein folding and directed evolution
Adopting and maintaining a properly folded proteome is critical for cellular function, and multiple diseases, most famously neurodegenerative disorders, have been linked to protein misfolding and disruption of proteostasis. Our group seeks to study and manipulate protein folding in cells to better understand the relationships between protein folding, evolution, and cellular fitness. By using genetically encoded biosensors to detect protein folding states, we can examine the factors that influence misfolding and select for biomolecules that inhibit protein aggregation.
Directed evolution is a powerful technique that can enable the identification of biomolecules with improved or novel function without prior information on structure or mechanism. Our group works with phage-assisted continuous evolution (PACE), a technique that greatly accelerates the rate of evolution compared to conventional methods by mapping the steps of directed evolution onto the life cycle of filamentous bacteriophage. We employ PACE to (1) develop new ways to discover biosynthesized macrocyclic peptides that can be employed as chemical inhibitors or probes, and (2) to study the effects of fitness and environmental factors on protein evolution.