CAREER: Chemical Control of Plant-Microbe Interactions

该研究计划的目标是开发新的化学方法，这些方法将广泛应用于合成和组合化学领域，并产生用于解剖细菌通信途径的化学工具。这些研究将揭示植物相关细菌群体感应激活或失活所必需的分子水平特征，并且开发的化学工具将为我们对植物-微生物相互作用的不断发展的理解提供新的见解。将开发一个化学教学实习项目，作为全国其他项目的原型，其目标是制定一个总体战略，以吸引和培养未来的化学科学教师。通过美国国家科学基金会资助的研究、教学和学习整合中心（CIRTL）和威斯康星大学麦迪逊分校的三角洲项目提供的基础设施、支持和宣传，将为建立这个实习项目提供坚实的基础。这个职业奖来自有机和大分子化学项目，支持威斯康星大学化学系海伦·e·布莱克威尔教授的研究。该研究计划的总体目标是设计、合成和评估调节植物相关细菌通讯机制的新型化学诱导剂。细菌用于交流的“语言”是可扩散的小分子（或“自诱导剂”），这种语言被它们的同源蛋白质受体感知。细菌利用这种化学语言来评估当地的种群密度，这一过程被称为“群体感应”。植物相关细菌使用群体感应来调节对其植物宿主有害和有益的关键过程。现在很明显，某些植物宿主反过来会“倾听”这些细菌信号，并用它们自己的化学信号做出反应。这个复杂的原核/真核生物通信网络的阐明将代表一个根本性的科学进步。细菌和植物对小分子语言的依赖使有机化学家处于一个独特的位置，可以揭示这种通信网络的基本原理，并设计新的工具来在分子水平上调节它。控制植物相关细菌群体感应的方法将对农业科学产生重大影响，因为全世界50%的作物疾病是由细菌群体感应调节行为引起的。此外，抑制细菌群体感应的分子代表了一种全新的抗感染药物，可能对人类健康产生直接影响。Blackwell教授还在追求一种策略，在教学即研究的概念的推动下，将实质性的教学实习与开发新的“主动学习”本科有机化学教学材料相结合，将有效的教学实践培训融入研究生和研究生的经验中。

This research program targets the development of new chemical methodology that will be of wide utility to the synthetic and combinatorial chemistry community and the generation of chemical tools for the dissection of bacterial communication pathways. The molecular level features that are essential for quorum sensing activation or inactivation in plant-associated bacteria will be revealed by these studies, and the chemical tools that are developed will provide new insights into our evolving understanding of plant-microbe interactions. A chemistry teaching internship program will be developed to serve as a prototype for others nationwide, with the objective of developing a general strategy to engage and train future faculty in the chemical sciences. Infrastructure, support, and publicity made available through the NSF-funded Center for the Integration of Research, Teaching, and Learning (CIRTL) and the Delta Program on the UW-Madison campus will provide a strong foundation on which to build this internship program.This CAREER award from the Organic and Macromolecular Chemistry Program supports the research of Professor Helen E. Blackwell, of the Department of Chemistry at the University of Wisconsin. The broad goal of this research plan is the design, synthesis, and evaluation of new chemical inducers that modulate communication mechanisms in plant-associated bacteria. The 'language' that bacteria use for communication is diffusible small molecules (or 'autoinducers') and this language is perceived by their cognate protein receptors. Bacteria use this chemical language to assess local population densities in a process known as 'quorum sensing'. Plant-associated bacteria use quorum sensing to regulate critical processes both harmful and beneficial to their plant host. It is now evident that certain plant hosts, in turn, 'listen' to these bacterial signals and can respond with their own chemical signals. The elucidation of this complex prokaryotic/eukaryotic communication network would represent a fundamental scientific advance. The reliance of both bacteria and plants on a language of small molecules places organic chemists in a unique position to uncover the fundamental principles underlying this communication network and design new tools to modulate it at the molecular level. Methods to control bacterial quorum sensing in plant-associated bacteria would have a major impact on agricultural science, because 50% of crop disease worldwide is caused by quorum sensing regulated behaviors in bacteria. Further, molecules that inhibit bacterial quorum sensing represent an entirely new class of anti-infectives that could have immediate impact on human health. Professor Blackwell is also pursuing a strategy to integrate training in effective teaching practices into the graduate and postgraduate experience, driven by the concept of teaching-as-research and combining substantive teaching internships with the development of new 'active learning' instructional materials for undergraduate organic chemistry.