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

该奖项全部或部分根据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，并设在化学部，教授科林·金茨-汤普森和他的学生在罗格斯大学纽瓦克将研究细菌化学传感器阵列（CA），在调节信号转导途径的一个重要过程。 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组合，以帮助了解准确的细菌化学传感的分子基础。 此外，Kinz-Thompson教授还将实施一项计划，帮助科学领域代表性不足的学生扩大STEM领域的参与，包括让代表性不足的少数民族（URM）本科生参与计划中的研究，开发新课程，为不同的学生群体带来计算和生物物理技术，并启动一个创客实验室，将参与与STEM相关的推广到当地URM学校的孩子。Kinz-Thompson教授将开发一种单分子荧光共振能量转移测定法（smFRET）使用沿着自由能微扰（FEP）计算来量化细菌化学感受器的底物特异性的能量学和该化学感受器的配体结合位点之间的抗协同性机制。 也将使用类似的smFRET实验，沿着随机化学主方程模拟，以评估涉及周质结合蛋白的化学传感校正机制的有效性。 在最后的科学目标中，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建模来量化细菌化学传感器阵列的体内四级结构以及重塑其的调节反应的后续效果。沿着使本科生能够直接参与研究活动，努力教授编程，电子学，3D打印，和其他令人兴奋的技术在传统的化学课程之外，将使未来的跨学科科学交流，并鼓励更多的学生追求科学的职业生涯。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.