| Bacteria communicate with chemical signals in a process known as quorum sensing. This population density-dependent process involves the bacterial production, release and detection of structurally specific small molecules and enables the bacterial pathogen to regulate its virulence on a population-wide level. Using a variety of chemical and biological techniques, I have studied various quorum sensing systems in several bacteria, including Vibrio cholera and Pseudomonas aeruginosa. A key principle of this research involves the design, synthesis and testing of novel compounds for their biological activity. These molecules are typically based off of an initial lead target, which is often identified from a high-throughput screen and serves as a template for further optimization. Specifically, I have researched quorum sensing compounds that affect Hfq-RNA interactions in V. cholera, the LasR receptor in P. aeuruginosa and HapR in V. cholera. Taken together, the results of these studies provide a basis for future investigations involving quorum sensing, and demonstrate how organic chemistry can be employed to study these fascinating biochemical systems. |
