CAREER:New chemical tools to study c-di-GMP signaling in bacteria

凭借这一职业奖，有机和高分子化学项目以及细胞系统集群项目支持马里兰大学帕克分校的赫尔曼·O·辛蒂姆教授的研究。辛蒂姆教授将开发新的化学工具来研究细菌中的3‘-5’-环二鸟氨酸(c-di-GMP)信号。C-di-GMP是细菌中特有的一种常见的化学信使，在细菌生物膜的形成和各种细菌毒力相关因子的调节中发挥着核心作用。细菌中c-di-GMP信号的几个问题仍未得到解答。例如，调节细菌中c-di-GMP信号的环境线索，以及对c-di-GMP细胞内浓度波动做出反应的接头蛋白的身份，在很大程度上仍未确定。第一个目标是开发一种c-di-GMP荧光传感器。这种传感器将有助于在不同的环境信号和细胞内c-di-GMP浓度之间建立联系。其次，将使用一种新的固相方法来制备光亲和的c-di-GMP类似物，用于鉴定c-di-GMP接头蛋白。C-di-GMP结合蛋白的鉴定应该有助于解开c-di-GMP显然调控的复杂信号网络。辛蒂姆教授还将在马里兰大学设立四个珀西·朱利安本科生研究奖学金。这项研究奖学金将向科学界代表性不足的少数族裔开放。珀西·朱利安研究员将得到支持，在马里兰大学一名知名研究员的实验室进行研究。这一奖学金提供了在少数族裔学生职业生涯的早期阶段培养他们的机会，并鼓励这些学生考虑在科学领域工作。

With this CAREER Award, the Organic and Macromolecular Chemistry program and the Cellular Systems Cluster program are supporting the research of Professor Herman O. Sintim of the University of Maryland, College Park. Professor Sintim will develop new chemical tools to study 3'-5'-cyclic diguanylic acid (c-di-GMP) signaling in bacteria. C-di-GMP, a common chemical messenger present uniquely in bacteria, plays a central role in bacterial biofilm formation and regulation of virulence-related factors in diverse bacteria. Several questions remain unanswered in c-di-GMP signaling in bacteria. For example, the environmental cues that modulate c-di-GMP signaling in bacteria and the identities of the adaptor proteins that respond to fluctuations in intracellular concentration of c-di-GMP remain largely uncharacterized. The first objective is to develop a fluorescent sensor for c-di-GMP. Such a sensor will be useful for establishing a link between different environmental cues and the intracellular concentrations of c-di-GMP. Secondly, a new solid-phase methodology will be used to prepare photo-affinity c-di-GMP analogs for the identification of c-di-GMP adaptor proteins. The identification of c-di-GMP binding proteins should help unravel the complex signaling network that c-di-GMP apparently regulates.Professor Sintim will also establish four Percy Julian undergraduate research fellowships at the University of Maryland. This research fellowship will be open to underrepresented minorities in the sciences. Percy Julian fellows will be supported to conduct research in the laboratory of an established investigator at the University of Maryland. This fellowship provides the opportunity to nurture minority students at an early stage of their careers and encourage such students to consider a career in the sciences.