Yftah Tal-Gan: Developing peptide-based tools to study streptococcal quorum sensing
Title
Developing peptide-based tools to study streptococcal quorum sensing
Mentor
Department
Biosketch
Since joining Βι¶ΉΣ³», Yftah Tal-Gan, Ph.D., has established a chemical biology research program with the overarching goal of developing and utilizing peptide-based probes to study bacterial communication pathways and their role in bacterial pathogenesis and inter-species competition. This research program is multidisciplinary and spans from organic synthesis and analytical characterization, to biological screening, structural determination of biomacromolecules, and molecular microbiology. Current projects in the lab are funded by one National Institutes of Health (NIH) and one National Science Foundation (NSF) grant, and have resulted in more than 40 papers from the lab.
The Tal-Gan lab group explores Streptococcal quorum sensing through a multifaceted lens. Quorum sensing (QS) is a cell-cell signaling mechanism that enables bacteria to assess their cell density in a given environment; and at a high population density, synchronize the transcription of genes associated with group-behavior phenotypes. Streptococcal QS circuits are centered around the production, secretion, and detection of peptide signals (termed autoinducers). The peptide signal concentration is directly proportionate to the population density. As the bacteria reach a critical concentration indicative of a high population density, quorum sensing peptides activate a membrane-bound receptor leading to the transcription of group behavior genes. Because many pathogens utilize QS to initiate and synchronize their attack on the host, in a process called virulence, QS interference can be used to reduce or eliminate bacterial pathogenicity without leading to resistance.
Project overview
Our interdisciplinary work resides at the intersection of organic chemistry, biochemistry, microbiology and molecular biology. Our research efforts are focused on the development and analysis of peptide-based probes to study QS in streptococci. Using organic chemical methods, we have developed QS peptide analogs of native streptococcal QS peptides that effectively silence QS signaling. These molecules are potential candidates for therapeutic alternatives to antibiotics. Additionally, using structural determination and molecular biology approaches, we analyze and manipulate QS peptide molecules and circuitry to understand binding dynamics that mediate downstream bacterial virulence and survival processes. Finally, using immunological approaches, we investigate how these systems influence the behaviors of host immune cells.
In this project, the PREP undergraduate researcher will synthesize and purify peptide-based signal analogs of the streptococcal ComABCDE QS circuitry, termed competence stimulating peptide (CSP). The PREP undergraduate researcher will then assist in evaluating the biological activity of the different CSP analogs they produced to delineate structure-activity relationships and define the molecular interactions that govern signal-receptor binding. This information would then be used to design novel CSP-based QS modulators with desired activity profiles.
Pack Research Experience Program information and application