Large-scale efforts in genome sequencing have elucidated much of the “parts list” for thousands of species, but a general description of how genes collectively interact to produce functioning systems eludes us. We use statistical analysis of genome sequences drawn from thousands of organisms to distill out general patterns describing the organization of cellular systems and individual proteins. By examining the conservation and co-evolution of genetic information across species, we can understand which cellular components are critical, infer functional interactions, and identify modular gene groups.
An important aspect of the lab is experimentally testing these statistical models for their ability to explain, predict, and design cellular behaviors. To do this, our lab has developed an infrastructure that permits: (1) deep scanning mutagenesis of genes (2) genome-wide second site suppressor screens under varying environmental conditions, and (3) high throughput measurements of fitness and genetic epistasis with excellent accuracy. We are broadly interested in new techniques for studying molecular evolution and strategies for synthetic biology.