CAREER: The Bioorganic Investigation of Species-Specific Biofilm Modulators

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. William Wuest from Temple University to investigate the role species-specific natural products play in biofilm communities using an interdisciplinary approach comprised of synthetic, microbiological, and proteomic techniques. Bacterial communities are incredibly complex and dynamic. These communities, commonly referred to as biofilms, adversely impact both commercial interests and societal health. The inherent complexity of microbial biofilms and lack of scientific tools to interrogate these systems has limited both basic research and practical innovations. There is currently great interest in developing small molecules as chemicial biological tools to specifically alter such systems to aid in sorting out these processes. The proposed research will focus on naturally occurring materials that possess exquisite selectivity for one species of bacteria to better understand how they work. The multidisciplinary aspects of this program will allow graduate students and undergraduates to gain expertise in a broad range of modern research techniques. This project also integrates an outreach program to mentor inner-city Philadelphia elementary school students in preparation for the George Washington Carver Science Fair.Synthetic methods will be used to construct the natural products, analogs, and affinity probes for biological investigations and target identification. Affinity-based protein profiling will then be applied to determine the specific biological targets of these compounds providing insight into their mechanism of action. Concurrently, compounds will be tested both for their antimicrobial activity and their ability to specifically perturb bacterial biofilms. The identification of the mechanistic targets of these biofilm-modulating natural products seeks to increase our basic understanding of the biochemical processes of chemical signaling in bacterial biofilms.