Elucidating in vivo functions of hydrogen peroxide

阐明过氧化氢的体内功能

• 批准号: RGPIN-2019-06766
• 负责人: Hurd, Thomas
• 金额: $ 2.99万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716380
• 关键词: Elucidating; vivo; functions; hydrogen; peroxide

Essential to an organism's survival is its ability to restore and maintain tissue integrity following injury. One of the earliest and most crucial responses to injury is the production of the oxidant hydrogen peroxide (H2O2). It is often the case that free radicals and oxidants, such as H2O2, are harmful and toxic; however, under certain circumstances, such as injury, cells in our bodies generate oxidants for beneficial purposes, for example to repair damage and heal. Using genetic and biochemical approaches, the central objective of this research proposal is to uncover how H2O2 helps to restore tissue integrity upon injury and damage. Our first aim is to determine what triggers the generation of H2O2 upon injury. Cells have special type of enzymes they use to generate H2O2 in response to injury; however, how they know when to activate these enzymes remains unknown. Using powerful genetic approaches in the model organism, the fruit fly, we will determine how cells turn on this enzyme during injury. Our second aim is to understand how, once produced, H2O2 helps to restore and repair injury. A main proposed function for injury-induced H2O2 is to alert immune cells that injury has occurred and to attract them to the site of injury. Once at the site of injury, immune cells are essential to stave off infection and repair damage. How H2O2 alerts and attracts immune cells remains unknown. Using both genetic and biochemical approaches we will elucidate this critical and essential function of H2O2 in injury repair. Our research will beneficially impact Canadians in numerous ways, including by training highly qualified personnel, by developing Canada's research capacity, and through scientific knowledge advancement. This research program will elevate Canada as a hub for research innovation and excellence in the basic biomedical sciences and redox biology. In doing so it will stimulate economic and societal growth through the training and recruitment of world-class scientists.

生物体的生存关键在于其在损伤后恢复和维持组织完整性的能力。对损伤的最早和最关键的反应之一是氧化剂过氧化氢（H2 O2）的产生。通常情况下，自由基和氧化剂，如H2 O2，是有害和有毒的;然而，在某些情况下，如损伤，我们体内的细胞产生氧化剂用于有益的目的，例如修复损伤和愈合。使用遗传和生物化学方法，这项研究的中心目标是揭示H2 O2如何帮助恢复损伤和损伤后的组织完整性。 我们的第一个目标是确定是什么触发了损伤后H2 O2的产生。细胞具有特殊类型的酶，它们用于产生H2 O2以响应损伤;然而，它们如何知道何时激活这些酶仍然未知。在模式生物果蝇中使用强大的遗传方法，我们将确定细胞如何在损伤期间打开这种酶。 我们的第二个目标是了解H2 O2一旦产生，如何帮助恢复和修复损伤。损伤诱导的H2 O2的一个主要功能是警告免疫细胞损伤已经发生，并将它们吸引到损伤部位。一旦到达损伤部位，免疫细胞对于避免感染和修复损伤至关重要。H2 O2如何警告和吸引免疫细胞仍然未知。使用遗传和生物化学的方法，我们将阐明这一关键和必要的功能H2 O2损伤修复。 我们的研究将在许多方面对加拿大人产生有益的影响，包括培训高素质的人才，发展加拿大的研究能力，以及通过科学知识的进步。该研究计划将提升加拿大作为基础生物医学科学和氧化还原生物学研究创新和卓越的中心。在这样做的过程中，它将通过培训和招聘世界一流的科学家来刺激经济和社会增长。