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在开发基于荧光的方法来研究化学和生物系统，以及使用这些方法获得的基础知识的应用，以产生新的材料和诊断。我们能够合成具有理想的化学反应性和生物物理行为的定制荧光探针，然后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单个分子的能力。单分子光谱学领域已经从最初的生物物理现象研究发展到多相介质中反应的机械探索，包括表面和各种纳米复合材料/催化剂。最诱人的是最近在生物系统成像和催化剂表征方面的突破，这些突破具有“超分辨率”（超过衍射极限）和灵敏度。这些技术利用化学反应（荧光化合物）的荧光诱导/增强来可视化，绘制并最终了解微观和纳米级（十亿分之一米）水平上发生的事情。然而，这些技术大多限于光化学触发的荧光探针的子集（它们是物理旁观者-信标）。在仔细设计对感兴趣的反应性化学物质（活跃的参与者"化学耀斑"）作出反应的荧光化合物时，存在着询问生物系统和纳米材料的巨大机会。在即将到来的资助期内，我们将利用过去6年的进展以及超分辨率成像领域的最新发展，致力于解决3个相互关联的当代问题。(I)我们将设计和制备荧光探针，以监测脂质膜的氧化还原状态，并荧光亲电探针，以触发类似于脂质过氧化副产物的反应。我们的目标是建立活性氧（ROS）的化学和它们的生物学之间的关系。(II)我们将可视化，映射和研究生物系统和纳米材料中的关键氧化还原过程，实施我们新开发的探针，结合SMS和超分辨率成像策略。(III)我们将开发新的SMS策略，以探索超分子结构/纳米材料的结构和组装动力学，从而调整高产率和提高材料质量的条件。在这种情况下，我们的目标是获得关键的机械信息，并在适用时将其转化为更好的纳米材料的制造。总的来说，我们将获得新化合物的光化学/光物理学知识。我们将开发具有许多研究人员所寻求的功能的分子。化学选择性探针和成像方法学将使对与ROS产生相关的细胞功能和活性产生广泛影响的根本性转化发现成为可能。探针和成像方法也将为制备改进的纳米材料/超分子结构铺平道路。待开发的新成像技术将成为纳米科学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例子，探索独特的方法，并开发尖端的成像技术来了解化学和生物系统。