CAREER: The Bioorganic Investigation of Species-Specific Biofilm Modulators

通过这一奖项，化学系的生命过程化学计划资助坦普尔大学的William West博士，利用合成、微生物和蛋白质组技术组成的跨学科方法，研究特定物种的天然产品在生物膜群落中所起的作用。细菌群落是极其复杂和动态的。这些社区通常被称为生物膜，对商业利益和社会健康都有不利影响。微生物生物膜固有的复杂性以及缺乏科学工具来审问这些系统，限制了基础研究和实践创新。目前有很大的兴趣开发小分子作为化学生物学工具，专门改变这种系统，以帮助分类这些过程。拟议的研究将集中在对一种细菌具有精致选择性的天然材料上，以更好地了解它们是如何工作的。该计划的多学科方面将允许研究生和本科生在广泛的现代研究技术方面获得专业知识。该项目还整合了一个外展计划，指导费城市中心的小学生为乔治·华盛顿·卡弗科学博览会做准备。合成方法将用于构建用于生物学研究和目标识别的天然产物、类似物和亲和力探针。然后，将应用基于亲和力的蛋白质图谱来确定这些化合物的特定生物靶标，从而深入了解它们的作用机制。同时，将测试化合物的抗菌活性和专门扰乱细菌生物膜的能力。识别这些调节生物膜的天然产物的机制靶标，旨在增加我们对细菌生物膜中化学信号的生化过程的基本理解。

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.