Nuclear magnetic resonance study of membrane interactions: from intact microorganisms to model membranes

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Cell membranes are the first barriers encountered by drugs and contaminants and, as such, are targeted or traversed by bioactive molecules which can, as a result, alter their organization with critical consequences on the cell. The study of membrane interactions is thus important for research fields such as drug discovery and toxicology. The goal of our research program is to study, using solid-state nuclear magnetic resonance (SS-NMR), the interaction of drugs and contaminants with membranes of intact microorganisms and to complement these studies by looking at specific interactions with selected membrane components using corresponding models. Specifically, the effect on antibiotics will be tested on human pathogens and marine bacteria, while the interaction of contaminants will be evaluated on marine microalgae. Novel membrane mimetics will be developed and characterized to scrutinize the response of specific biomembrane constituents. In vivo investigations will be performed using isotopic labeling of the cells and sophisticated NMR experiments selecting signals from dynamic membrane constituents. This program is innovative since it extends the emerging field of in vivo NMR to the study of membrane interactions to which very few research groups in the world have contributed. Another original aspect is to tackle membrane interactions with marine organisms. This research is highly important as it provides new tools for developing novel antibiotics, necessary in the face of worldwide emergence of bacterial resistance. It will also evidence the impact of water pollution on the marine microorganisms due to increasing human and industrial activities associated with fast population growth. With global warming, pathogens prone to multi-drug resistance are increasingly threatening humans as well as the water biota including species from aquaculture - a growing commercial activity in Canada. Phytoplankton is considered as a potential biofuel resource as well as being a prospective feeding solution to the growing problem of malnutrition worldwide. The in vivo study of algal cells which support the aquatic food chain will improve our understanding of pollutants' action and their transfer to higher organisms.