Cellular & Molecular Engineering Laboratory

Michelle O'Malley

Education
PhD candidate in Chemical Engineering, University of Delaware, Newark, DE
Thesis Advisor: Dr. Anne Skaja Robinson

B.S. Chemical Engineering, Carnegie Mellon University, 2004

B.S. Biomedical Engineering, Carnegie Mellon University, 2004

Research:

The G-protein coupled receptors (GPCRs) are 7-transmembrane domain proteins which reside within the plasma membrane of the cell. Typically, they bind a small molecule ligand (ie. hormones, peptides, etc.) outside the cell which induces a conformational change within the cell, causing a specific cellular response to occur. Since GPCRs are largely responsible for cellular communication, they have emerged as attractive drug targets with greater than 50% of pharmaceuticals on the market targeting these proteins. Even though GPCRs have been the focus of therapeutics for some time, relatively little is known about their interactions and detailed structure. Unfortunately, membrane proteins have proven notoriously difficult to study owing to problems with their overexpression, purification, and maintenance of proper structure in vitro. My research interests involve using a previouisly-established yeast expression system to produce and purify mammalian G-protein coupled receptors, specifically of the adenosine-binding family. After sufficient purification is achieved, I also plan to explore the effect of surfactant and lipid additives on folding and activity of isolated receptors. Further biophysical characterization of these GPCRs in vitro will provide more detailed information on their folding and stability, and ultimately contribute to high-resolution structure determination through X-ray crystallography or NMR. Also, as heterologous expression of GPCRs in yeast is not completely understood, I would like to identify and alleviate expression bottlenecks in yeast for mammalian GPCRs. This work will lead to the development of a yeast expression system for the systematic production and purification of mammalian GPCRs, ultimately leading to high-resolution structure determination of GPCRs that will contribute to structure-based drug design.

General contact information for: Michelle O'Malley

Group Contact