LEAPS-MPS: Accuracy and the Regulatory Reprogramming of Bacterial Chemosensing

该奖项全部或部分由《2021年美国救援计划法案》（公法117-2）资助。在这个项目中，由数学和物理科学理事会资助，位于化学部门，罗格斯大学纽瓦克分校的Colin Kinz-Thompson教授和他的学生将研究细菌化学感觉阵列（CA），这是调节信号转导途径中的一个重要过程。Kinz-Thompson教授将开发先进的光谱学和显微镜技术以及复杂的计算建模方法的结合，以帮助理解准确的细菌化学传感的分子基础。此外，Kinz-Thompson教授将实施一项计划，帮助在科学领域代表性不足的学生扩大对STEM领域的参与，包括让代表性不足的少数族裔（URM）本科生参与计划中的研究，开发新课程，将计算和生物物理技术引入不同的学生群体，以及启动一个创客实验室，参与与STEM相关的外展活动，为当地URM学生提供服务。Kinz-Thompson教授将开发一种单分子荧光共振能量转移测定（smFRET），与自由能摄动（FEP）计算一起用于量化细菌化学受体底物特异性的能量学以及该化学受体配体结合位点之间的抗协同作用机制。类似的smFRET实验也将与随机化学主方程模拟一起使用，以评估涉及质周结合蛋白的化学感觉校对机制的有效性。在最终的科学目标中，Kinz-Thompson教授将使用荧光超分辨率显微镜和基于贝叶斯推理的模型来量化细菌化学感觉阵列的体内四级结构以及随后的调节反应对其进行重塑的影响。除了允许本科生直接参与研究活动外，努力教授传统化学课程之外的技能，如编程、电子、3D打印和其他令人兴奋的技术，将使未来的跨学科科学交流成为可能，并鼓励更多的学生从事科学事业。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). In this project, funded by the Mathematical and Physical Sciences Directorate and housed in the Chemistry Division, Professor Colin Kinz-Thompson and his students at Rutgers University Newark will study the bacterial chemosensory array (CA), an important process in regulatory signal transduction pathways. Prof. Kinz-Thompson will develop a combination of advanced spectroscopy and microscopy techniques and sophisticated computational modeling approaches to help understand the molecular basis of accurate bacterial chemosensing. In addition, Prof. Kinz-Thompson will implement a plan to help broaden participation in STEM fields by students underrepresented in the sciences, including involving underrepresented minority (URM) undergraduate students in the planned research, developing new courses to bring computational and biophysical techniques to a diverse group of students, and starting a maker lab that will participate in STEM-related outreach to local URM school children.Professor Kinz-Thompson will develop a single-molecule fluorescence resonance energy transfer assay (smFRET) to use along with free energy perturbation (FEP) calculations to quantify the energetics of substrate specificity for a bacterial chemoreceptor and the mechanism of anti-cooperativity between the ligand binding sites of that chemoreceptor. Similar smFRET experiments will also be used, along with stochastic chemical master equation simulations, to evaluate the effectiveness of a chemosensory proofreading mechanism involving periplasmic binding proteins. In a final scientific aim, Prof. Kinz-Thompson will use fluorescence super-resolution microscopy and Bayesian inference-based modeling to quantify the in vivo quaternary structure of the bacterial chemosensory array and the subsequent effect of a regulatory response that remodels it. Along with enabling direct participation of undergraduate students in research activities, efforts to teach skillsets such as programing, electronics, 3D printing, and other exciting techniques outside of traditional chemistry curricula will enable future interdisciplinary scientific exchanges and encourage more students to pursue careers in science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.