- Professor Dept. of Biochemistry and Molecular Biology, University of Chicago
Department of Biochemistry and Molecular Biology
The University of Chicago
929 East 57th Street, CIS W210
Chicago, IL 60637
Phone: 773 702 9257
Fax: 773 702 9257
1) One of our research interests centers around studying at atomic resolution the structural and functional properties that define molecular recognition systems that activate and regulate biological properties. In particular, we study the energetics of hormone-induced receptor activation and regulation of growth hormone and its receptor using X-ray crystallography, site-directed mutagenesis, phage display mutagenesis and biophysical analysis. We are asking two fundamental questions: What are the mechanisms and the energetics involved in the binding of a hormone to a cell-surface receptor that trigger biological responses in the cell? How can related hormones show both the binding versatility and finely honed specificity required for biological regulation? Using phage display we have discovered an allosteric coupling between the two receptor binding sites on growth hormone, and have produced growth hormone variants that work through a drastically reduced binding interface.
2) Chaperone-assisted crystallography- We use antibody engineering to produce antibody- protein complexes to facilitate crystallization of membrane proteins, functional RNAs and protein complexes that are recalcitrant to convention crystallization. Our engineering techniques are based on novel phage display libraries that use a reduced genetic code.
3) Functional fishing- We use enzyme active site affinity tags to isolate novel enzymes that are unique to organisms that live in extremely harsh environments. We are trapping and structurally characterizing DNA- repair enzymes that function under high radiation conditions.
4) Synthetic biology- We use a combination of peptide synthesis and phage display (biosynthetic phage display) to produce proteins with novel properties.