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

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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.