Molecular Forces in Microbial Biofilms

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This NSERC discovery grant proposal seeks to discover mechanisms underlying the molecular forces that stabilize microbial biofilm formation on a wide variety of surfaces. Microbial biofilms play a central role in most major fouling problems in several sectors in Canada (e.g. food safety, agriculture, industrial and oil pipelines, ship hull coatings etc.), and is estimated to cost billions of dollars annually. A key reason behind this growing biofilm-related problems is our limited understanding of the mechanisms by which bacteria adhere to a wide range of surfaces, and the lack of molecular understanding behind the forces responsible for stabilizing these biofilms. As initial adhesion and microcolony formation of bacteria on surfaces are crucial pre-requisites for mature biofilms, this research program will target the initial stages of biofilm formation, and will focus on the “molecular forces” that confer biofilm stability during these critical phases of biofilm development. In particular, it aims to dissect the nanoscopic interplay between bacteria's surface adhesion molecules and the properties of the underlying substrate, initially addressing the influence of substrate stiffness on the growth of E. coli biofilms.While substrate stiffness has long been established to influence mammalian cell signalling and stem cell differentiation, its influence on microbial biofilm growth is rather a recent discovery and is not yet well understood. In order to fill the gap on how substrate stiffness affects the molecular forces that stabilize biofilms, my lab will pioneer a three-way correlated measurements between scanning probe microscopy, optical microscopy, and force spectroscopy, with single-molecule and single-cell resolution. This quantitative and correlated approach to biofilm study will not only provide high-resolution images of the biofilm's complex structures, under physiological conditions, it will also quantify the nanoscale forces that stabilize these structures. The long-term goal is to expand the research to cover other substrate properties, and other biofilm-forming bacteria. This will provide a more general mechanistic insights into how the physico-chemical characteristics of the substrate influence the molecular forces that confer biofilm stability.Results from this research program will not only further our mechanistic understanding of the biofilm's structural stability in adhering to different surfaces, it will also lead to tangible benefits to Canadian industries related to agriculture, energy, environment, and public health, and to the global population, especially with the growing threat of antimicrobial-resistant organisms. Furthermore, with the interdisciplinary nature of the research it will be an excellent training ground for the next generation of Canadian scientists, and will bring Canada at the forefront of quantitative biofilm research.