Credentials: Biochemistry Department
Position title: Synthetic biology, protein design, metabolic engineering, allostery, directed evolution
Phone: (608) 890-1036
433 Babcock Dr
Madison, WI 53706
Molecular & Genome Biology of Microbes; Systems Biology
Our laboratory takes a systems approach to designing new proteins, understanding mechanism of protein function, studying evolution of proteins and applying designer proteins to solve synthetic biology challenges. We combine state-of-the-art protein modeling tools (Rosetta) with high-throughput experimental phenotyping methods to addresses these questions. In particular, our lab focuses on allosteric transcription factors because they are small-molecule sensors that function as biological switches. These small molecule sensors are widely needed in synthetic biology for construction of biosynthetic pathways, regulation of endogenous or synthetic gene circuits, environmental sensing and real-time monitoring of in-situ metabolite concentration. With allosteric TF as a model system, we are interested in studying how allostery works at molecular resolution. Our current understanding of allostery is largely limited to biophysical models that explain conformational transitions between allosteric states, without knowledge of the amino acid network that communicates the allosteric signal. Our objective is to understand the general principle of protein structure that underlies the process of allosteric communication at molecular resolution. We will use high-throughput, protein-wide mutational screens coupled with next generation sequencing to functionally characterize millions of mutants of a candidate protein. We will combine mutational data with computational stability calculations and biophysical measurements to elucidate the allosteric network.