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个障碍，因此是生物活性分子的靶标或穿透，从而可能改变其组织结构，对细胞造成严重后果。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。我们研究计划的目标是使用固体核磁共振(SS-核磁共振)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观察与选定膜组分的特定相互作用来补充这些研究。具体地说，将测试抗生素对人类病原体和海洋细菌的影响，同时将评估污染物对海洋微藻的相互作用。新的膜模拟物将被开发和表征，以考察特定生物膜成分的响应。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，从动态的膜成分中挑选信号。这个项目是创新的，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。另一个原创性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，因为它为开发新的抗生素提供了新的工具，面对全球出现的细菌耐药性是必要的。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，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越来越多地威胁着人类以及包括水产养殖物种在内的水生生物--这在加拿大是一种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潜在饲料解决方案。对支持水生食物链的藻类细胞进行体内研究，将有助于我们更好地了解污染物的作用及其向高等生物的转移。

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.