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

细胞膜是药物和污染物遇到的第一道屏障，因此，生物活性分子可以靶向或穿越细胞膜，从而改变它们的组织，对细胞产生严重后果。因此，膜相互作用的研究对药物发现和毒理学等研究领域具有重要意义。我们的研究计划的目标是使用固态核磁共振（SS-NMR）来研究药物和污染物与完整微生物膜的相互作用，并通过使用相应的模型来观察与选定膜组分的特定相互作用来补充这些研究。具体而言，将在人类病原体和海洋细菌上测试抗生素的影响，而在海洋微藻上评估污染物的相互作用。新的膜模拟物将被开发和表征，以仔细审查特定生物膜成分的反应。体内研究将使用细胞的同位素标记和复杂的核磁共振实验从动态膜成分中选择信号。该计划具有创新性，因为它将体内核磁共振的新兴领域扩展到膜相互作用的研究，而世界上很少有研究小组对此做出贡献。另一个原始的方面是解决膜与海洋生物的相互作用。这项研究非常重要，因为它为开发新型抗生素提供了新的工具，这是面对世界范围内细菌耐药性出现所必需的。它还将证明由于与人口快速增长相关的人类和工业活动的增加而造成的水污染对海洋微生物的影响。随着全球变暖，容易产生多重耐药性的病原体正日益威胁着人类以及水生生物群，包括来自水产养殖的物种——这是加拿大日益增长的商业活动。浮游植物被认为是一种潜在的生物燃料资源，也是解决全球日益严重的营养不良问题的一种有前景的饲料解决方案。支持水生食物链的藻类细胞的体内研究将提高我们对污染物的作用及其向高等生物转移的理解。

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.