Chemical and biological processes studied with advanced imaging techniques

使用先进的成像技术研究化学和生物过程

• 批准号: RGPIN-2014-03587
• 负责人: Cosa, Gonzalo
• 金额: $ 6.12万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=648117
• 关键词: Chemical; biological; processes; studied; advanced

Our research program centres on the development of fluorescence-based methodologies to study chemical and biological systems, and on the application of the fundamental knowledge gained using these methods to generate novel materials and diagnostics. We are able to synthesize customized fluorescent probes with desirable chemical reactivity and photophysical behaviour, and to then develop and exploit state-of-the-art single molecule fluorescence imaging methodologies with them, in our pursuit of the mechanistic underpinning of complex systems. **Fundamental to our research work is our ability to monitor single molecules in action. The field of single molecule spectroscopy has evolved from its original focus on the study of biophysical phenomena, to mechanistic exploration of reactions in heterogeneous media, both on the surface and within a diverse range of nanocomposite materials/catalysts. Most tantalizing are recent breakthroughs in the imaging of biological systems and characterization of catalysts at work with "super resolution" (beyond diffraction limit) and sensitivity. These techniques exploit the induction/enhancement of fluorescence upon a chemical reaction (fluorogenic compounds) to visualize, map and ultimately understand what occurs at the microscopic and nanoscopic (a billionth of a meter) level. The techniques are however mostly limited to a subset of fluorogenic probes that are photochemically triggered (they are physical spectators - beacons). Tremendous opportunities exist to interrogate biological systems and nanomaterials upon careful design of fluorogenic compounds that respond to reactive chemical species of interest (active players "chemical flares").**In the coming grant period we will capitalize on our progress of the past 6 years and on recent developments in the field of super resolution imaging working on 3 interrelated contemporary problems. (I) We will design and prepare fluorogenic probes to monitor the redox status of lipid membranes and also fluorogenic electrophilic probes to trigger reactions akin to those observed with by-products of lipid peroxidation. Our goal is to establish the relationship between the chemistry of reactive oxygen species (ROS) and their biology. (II) We will visualize, map and study key redox processes both in biological systems and nanomaterials implementing our newly developed probes, combining SMS and incorporating super resolution imaging strategies. (III) We will develop new SMS strategies to explore the structure and the assembly dynamics of supramolecular structures/nanomaterials tuning conditions for high yields and improved quality materials. Our goal in this case is to gain key mechanistic information and translate it to the manufacture of better nanomaterials when applicable.**In general, we will gain knowledge on the photochemistry/photophysics of new compounds. We will develop molecules that have functions that many researchers seek. The chemoselective probes and imaging methodologies will enable fundamental transforming discoveries of broad impact on cell function and activity correlated with ROS production. The probes and imaging methods will also pave the way to prepare improved nanomaterials/supramolecular structures. New imaging technologies to be developed will become the standards of quality and structural characterization in nanoscience. **Our program will provide landmark examples where unique approaches are explored and cutting-edge imaging technologies are developed toward understanding chemical and biological systems.

我们的研究计划集中于研究化学和生物系统的基于荧光的方法，以及使用这些方法获得的基本知识的应用来生成新型材料和诊断。我们能够使用理想的化学反应性和光物理行为合成定制的荧光探针，然后与它们一起开发和开发和利用最先进的单分子荧光成像方法，以追求复杂系统的机械基础。 **我们的研究工作的基础是我们监测行动中的单分子的能力。单分子光谱的领域已经从其对生物物理现象的研究的最初关注，转变为在表面和各种纳米复合材料/催化剂范围内的异质培养基中反应的机械探索。大多数诱人的是在生物系统成像中的最新突破，并且具有“超级分辨率”（超出衍射极限）和灵敏度的催化剂表征。这些技术利用化学反应（荧光化合物）对荧光的诱导/增强，以可视化，映射并最终理解微观和纳米镜面（十亿分之一）水平的情况。但是，这些技术主要限于光化学触发的荧光探针的一部分（它们是物理观众 - 信标）。在仔细设计荧光化合物时，存在巨大的机会，可以质疑生物系统和纳米材料，这些化合物响应了对反应性化学物种感兴趣的化学物种（活跃的玩家“化学弹力”）。 （i）我们将设计和准备荧光探针，以监测脂质膜的氧化还原状态以及荧光亲电探针，以触发类似于脂质过氧化副产品观察到的反应。我们的目标是建立活性氧（ROS）的化学关系与其生物学之间的关系。 （ii）我们将在生物系统和实施新开发的探针，结合SMS并结合超级分辨率成像策略的生物系统和纳米材料中可视化，映射和研究关键的氧化还原过程。 （iii）我们将制定新的SMS策略，以探索超分子结构/纳米材料调整条件的结构和组装动力学，以实现高产量和改善的质量材料。在这种情况下，我们的目标是获取关键的机械信息，并将其转化为适用的更好的纳米材料的生产。我们将开发具有许多研究人员寻求的功能的分子。化学选择性探针和成像方法将使对细胞功能的广泛影响和与ROS产生相关的活性的基本转化。探针和成像方法还将为准备改进的纳米材料/超分子结构铺平道路。要开发的新成像技术将成为纳米科学中质量和结构表征的标准。 **我们的计划将提供具有里程碑意义的示例，其中探索了独特的方法，并开发了用于理解化学和生物系统的尖端成像技术。