Bioinorganic Chemical Biology

生物无机化学生物学

• 批准号: RGPIN-2014-03783
• 负责人: Bohle, David
• 金额: $ 3.13万
• 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: 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=632692
• 关键词: Bioinorganic; Chemical; Biology

Although there are many motivations and definitions of chemical biology the one that drives the program of research in my laboratory is that it is a theme and an approach "to discover new chemistry." Our unifying guiding hypothesis is global, open-ended, and invigorating; by understanding how biological evolution has circumvented the fundamental chemical limitations imposed by terrestrial temperature, pressure, environment, and element distribution considerable new chemistry can be discovered. This approach allows for discovery and innovation in that not only are new techniques and tools used, and developed, to help solve important health related problems, but solutions to deeper scientific issues are uncovered. Current chemical biology research in the Bohle group follows three general themes: A; the first is related the unusual biochemistry often employed by parasites, with the heme metabolism in pathogens such as plasmodia (malaria), B; the bioinorganic chemistry of rarely utilized elements such as arsenic and tungsten, and C; the final area to the study of bio-inspired nitrogen chemistry. A. Parasites such as plasmodia have a highly evolved biology which allows them to have some of the most complicated life cycles and often have elegant biochemistry. Often they have sophisticated means to circumvent the host’s immune system; they are a logical place to apply the ideas of chemical biology. B. The biochemistry of underutilized elements remains a challenging area of chemical biology. Elements such as tungsten and arsenic are in fact relatively common and available, and yet evolution has rarely used either of them in any context. Our research into these topics is highly collaborative and at present focusses on their toxicology and medicinal value. Finally C, few first row elements have the remarkably variable oxidation state chemistry of nitrogen and its oxides. If we can understand how the nitrogen oxides are employed in organisms we can in principle use these ideas in commercial/industrial settings especially for pollution abatement strategies. Our approach to this research is to work on the fundamental problems in each of these themes. This style is ideally suited for the training of HQP and it does not tie us to a particular technique, method, or class of compounds. To illustrate this diversity my group can frequently be found working at Synchrotrons as well as preparing and characterizing new compounds. For the latter we use a wide range of spectroscopic and structural techniques, with X-ray diffraction being particularly useful. Theoretical methods are also drawn upon for both their predictive and supporting roles. At its best our work is highly collaborative with our chemistry having value for biologists and clinicians as well stimulating our efforts in bioinorganic chemical biology.

尽管化学生物学有许多动机和定义，但推动我实验室研究计划的一个因素是，它是一个主题和一种方法，“发现新的化学。“我们的统一指导假设是全球性的，开放式的，令人振奋的;通过了解生物进化如何规避地球温度，压力，环境和元素分布所施加的基本化学限制，可以发现相当多的新化学。这种方法允许发现和创新，因为不仅使用和开发新技术和工具来帮助解决重要的健康相关问题，而且还发现了更深层次的科学问题的解决方案。目前在Bohle组的化学生物学研究遵循三个一般主题：A;第一个是相关的不寻常的生物化学经常采用寄生虫，与血红素代谢的病原体，如疟原虫（疟疾），B;生物无机化学很少使用的元素，如砷和钨，和C;最后一个领域的生物启发氮化学的研究。A.疟原虫等寄生虫具有高度进化的生物学，这使得它们具有一些最复杂的生命周期，并且通常具有优雅的生物化学。它们通常有复杂的手段来绕过宿主的免疫系统;它们是应用化学生物学思想的逻辑场所。B。未充分利用元素的生物化学仍然是化学生物学的一个具有挑战性的领域。钨和砷等元素实际上是相对常见和可用的，但进化很少在任何情况下使用它们中的任何一个。我们对这些主题的研究是高度合作的，目前主要集中在毒理学和药用价值上。最后C，少数第一行元素具有氮及其氧化物的显着可变的氧化态化学。如果我们能够理解氮氧化物是如何在生物体中使用的，我们原则上可以在商业/工业环境中使用这些想法，特别是在污染减排策略中。我们的研究方法是研究这些主题中的每个主题的基本问题。这种风格非常适合HQP的培训，它不会将我们束缚在特定的技术，方法或化合物类别上。为了说明这种多样性，我的团队经常在同步加速器工作，以及制备和表征新化合物。对于后者，我们使用广泛的光谱和结构技术，X射线衍射特别有用。理论方法也借鉴了他们的预测和支持作用。在最好的情况下，我们的工作与我们的化学高度合作，对生物学家和临床医生有价值，并刺激我们在生物无机化学生物学方面的努力。