Dr. Michael A. Weiss

Areas of Research 

Proteien engineering with application to (a) insulin analogs and glucose-responsive insulins (GRIs): and (b) specific DNA-bending proteins to regulate developmental gene expression in "genomic engineering."

Projects

(a) Our laboratory at the IU School of Medicine (IUSM) has been involved in the structural optimization of insulin molecules by protein engineering. A key example is provided by stabilization via halogen-modified aromatic-aromotic interactions. Insulin's dimer assembly stabilizes the self-assembly and modification of the critical residues at this interface provide highly stable molecules for therapeutic applications. GRI's define a novel class of therapeutic analogs that are inactive at normal glucose levels, but become active at higher glucose levles as seen in patients with diabetes. Such a designis may be provided by chemical glucose sensor at one end of insulin molecule and diol molety on the other end. 

 

(b) Our lab is also interested in studying DNA-bending proteins such as SRY high mobility box (HMG). Protein engineering enabled by native chemical ligation provides access to unnatural mutagenesis of key residues to probe structural details. SRV's cantilever provides such an opportunity to study the crucial role of isoleucine in the DNA bending. 

Recruitment Needs