Developmental regulation of mitochondrial RNA editing in trypanosomes

锥虫线粒体RNA编辑的发育调控

• 批准号: RGPIN-2016-05361
• 负责人: Salavati, Reza
• 金额: $ 2.77万
• 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=664122
• 关键词: Developmental; regulation; mitochondrial; RNA; editing

Trypanosomatid species are related parasitic unicellular organisms that are responsible for serious human diseases such as African sleeping sickness, Chagas' disease, and leishmaniasis. Trypanosoma brucei for instance is a bloodstream, extracellular pathogen that affects the central nervous system and causes human sleeping sickness. T. brucei mortality rate alone is 48,000 individuals per year and has an annual loss of 1.5 million disability-adjusted life years (DALYs). These diseases have also been introduced to the western world by blood transfusion and organ donation of immigrants and returning soldiers. The survival of this vector-borne parasite through its intricate life cycle is extensively dependent on the fine regulation of hundreds of genes. This includes, differential expression of their mitochondrial genes, representing a highly diverged system from those of mammals (hosts) or other metazoan and protozoan organisms. We hypothesize that understanding the regulation of gene expression in these lethal pathogens is essential to understanding their biology and identification of key regulatory modules (likely drug targets) that may be shared in multiple trypanosomatid pathogens. In the short term, this research will identify and characterize the essential factors (regulators) responsible for differential mechanisms of ATP generation during the life-stages of T. brucei. For this purpose, we will use our computational tools along with experimental approaches to identify factors that modulate the events during transition. The long term goal of this research is to provide a global map of the molecular network that regulates the energy production. As this network plays indispensable roles in transmission, infectivity and disease, this project will pave the way for much needed future therapeutics against trypanosomatids.**

锥虫是一种相关的寄生单细胞生物，可引起严重的人类疾病，如非洲昏睡病、恰加斯病和利什曼病。例如，布氏锥虫是一种血液、细胞外病原体，影响中枢神经系统并引起人类昏睡病。T.仅布鲁氏病死亡率一项，每年就有48 000人死亡，每年损失150万残疾调整生命年。这些疾病也通过移民和归国士兵的输血和器官捐赠传入西方世界。这种媒介传播的寄生虫在其复杂的生命周期中的生存广泛依赖于数百个基因的精细调控。这包括它们的线粒体基因的差异表达，代表了与哺乳动物（宿主）或其他后生动物和原生动物生物体的线粒体基因高度分化的系统。我们假设，了解这些致命病原体的基因表达调控是必不可少的了解其生物学和识别的关键调控模块（可能的药物靶点），可能会在多种锥虫病原体共享。在短期内，这项研究将确定和表征的基本因素（监管机构）负责不同机制的ATP产生在生命阶段的T。布鲁塞。为此，我们将使用我们的计算工具沿着与实验方法，以确定在过渡过程中调节事件的因素。这项研究的长期目标是提供一个调节能量产生的分子网络的全球地图。由于该网络在传播，传染性和疾病中发挥着不可或缺的作用，该项目将为未来急需的锥虫治疗铺平道路。