Research

Research Interests: Chemical Biology, Bioorganic Synthesis, Quorum Sensing, Bacterial-Eukaryotic Communication, Molecular Basis of Pathogenesis

Quorum Sensing

An important focus of my research will be the study of bacterial intra- and interspecies signaling molecules. Cell-to-cell communication is used by single-cell organisms to coordinate their behavior and function in such a way that they can adapt to changing environments and possibly compete with multicellular organisms. Chemical communication amongst bacteria has been termed “quorum sensing” (QS). Examples of QS-controlled behaviors are biofilm formation, virulence factor expression, antibiotic production and bioluminescence. These processes are beneficial to a bacterial population only when they are carried out in a coordinated fashion. Quorum sensing systems exist in both gram-positive and -negative bacteria and a variety of oligopeptides and N-acyl-homoserine lactones have been identified as QS molecules. Many QS molecules have not been characterized fully, and we will attempt to clarify the role of various QS molecules in bacterial signaling (in species such as Vibrio cholerae, Salmonella typhimurium, Helicobacter pylori) through synthesis and evaluation of QS molecules and potential antagonists and we will develop methodologies to study a wide variety of newly discovered and undiscovered QS molecules.

Examples of QS molecules employed by pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus

Bacterial-Eukaryotic Interkingdom Signaling

Recent reports have shown that several QS molecules can also have a direct effect on eukaryotes. The prime area of interactions between QS signals and higher organisms is presumed to be the innate immune system, whose main function is to detect the presence of invading micro-organisms and viruses. It is very likely that eukaryotes have developed mechanisms to sense the QS molecules that bacteria use to assess their cell density, since that would enable a rapid response that is correlated with the size of the bacterial population. We will investigate the interactions between QS molecules and potential receptors in eukaryotes that are expected to trigger an immune response. These investigations will further our understanding of the complex interactions that exist between bacteria and humans, and of certain mechanisms that the immune system uses to control both benign and pathogenic bacterial populations.