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

膜相互作用的核磁共振研究：从完整的微生物到模型膜

• 批准号: 326750-2013
• 负责人: Marcotte, Isabelle
• 金额: $ 3.21万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632524
• 关键词: Nuclear; magnetic; resonance; study; membrane

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.

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过细胞膜，从而改变它们的组织，对细胞产生严重影响。因此，膜相互作用的研究对于药物发现和毒理学等研究领域非常重要。我们的研究计划的目标是研究，使用固态核磁共振（SS-NMR），药物和污染物与完整微生物的膜的相互作用，并通过使用相应的模型与选定的膜组件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，而污染物的相互作用将在海洋微藻上进行评估。新型膜模拟物将被开发和表征，以仔细检查特定生物膜成分的响应。体内研究将使用同位素标记的细胞和复杂的NMR实验选择信号的动态膜成分。该计划具有创新性，因为它将体内NMR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，这是面对全球范围内出现的细菌耐药性所必需的。它还将证明由于与人口快速增长相关的人类和工业活动增加而造成的水污染对海洋微生物的影响。随着全球变暖，易于产生多药耐药性的病原体日益威胁人类以及水生生物群，包括水产养殖物种-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喂养解决方案。对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。