CAREER: Nanomechanics of Bacterial Mucoadhesion and Growth on Healthy and Diseased Human Gut Mucus

Cornell University, Ithaca NY

Investigators

Abstract

This Faculty Early Career Development (CAREER) award will support fundamental research to determine how differences in the molecular structures of healthy and diseased mucus in the human gut can alter the adhesion of bacteria on mucus. Intestinal mucus is the first line of microbial defense. A wide range of human gut disorders can be caused by biofilm invading the mucus. This is a challenging problem to study due to complex interlinked factors of how mucus molecules assemble, how bacteria adhere to mucus, and how mucosal biofilm is shed in the human gut. This research project will use computational modeling and simulations to obtain nanoscale insights on these factors. These insights will help to accelerate the design of mucoadhesive therapeutics or antimicrobials for treating human gut disorders. The research program will also bridge pathways towards multidisciplinary graduate education for undergraduate students, especially from underrepresented groups, by integrating engineering, biological, and humanistic sciences through an online project-based summer course, the curriculum of the nonprofit educational organization, Station1, and the Cornell University’s Future Leaders in Aerospace and Mechanical Engineering (FLAME) program. The specific objectives of this research program are to use computational modeling and simulations to: 1) determine how the supramolecular assembly of mucins is altered by disease-related changes in glycan compositions and structures, and bacterial enzymatic degradation of glycans, 2) uncover the molecular mechanisms of bacterial adhesion on mucus surfaces, to investigate why glycan assemblies in enzymatically degraded and unhealthy mucins will have greatly differing bacterial binding characteristics compared to healthy mucins, and 3) unravel the effects of mucoadhesion on bacterial growth in mucus to probe how biofilms adhere to mucus and proliferate under the influence of mucus degradation and physiological mucus clearance. The mechanistic insights from this project will help to accelerate the design of mucoadhesive materials for drug delivery or antimicrobials for the human gut by revealing the supramolecular structures of mucus and their glycans, unraveling how bacteria recognize and adhere to highly heterogenous glycan domains, and determining how these differences in adhesive characteristics ultimately affect the shedding dynamics of mucosal biofilms. This project will also provide a critical steppingstone towards developing engineered living materials that specifically shapes the growth of biofilms for desired engineering purposes. 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.