Chemical Biology, Bioorganic Synthesis, Quorum Sensing, Bacterial-Eukaryotic Communication, Molecular Basis of Pathogenesis.
Microbial Chemical Communication and Quorum Sensing
An important focus of our group's research is 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. Population density-dependent 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 common structural motifs, including oligopeptides and N-acyl-homoserine lactones, have been identified as QS molecules. Many QS molecules have not been characterized fully, and we continuously aim to identify and clarify the role of various QS molecules in bacterial signaling (in species such as Pseudomonas aeruginosa, Staphylococcus aureus, Vibrio cholerae, Bacillus subtilis, etc.) through synthesis and evaluation of QS molecules and potential agonists and antagonists, and we develop methodologies to study a wide variety of newly discovered and undiscovered QS molecules.
Examples of QS molecules employed by pathogens such as P. aeruginosa, V. cholerae, E. faecalis and S. aureus
Bacterial-Eukaryotic Interkingdom Signaling
It has become clear in recent years that QS molecules can also have direct effects on eukaryotes. The prime area of interactions between QS signals and higher organisms (such as animals) 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 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 animals such as us, and of certain mechanisms that the immune system uses to control both benign and pathogenic bacterial populations.
Inspired by the pioneering work from the Dorrestein group on mass-spectrometry networking as a tool to...
We develop probes based on signaling molecules and use chemical proteomics methodologies...