mRNA-binding proteome in Trypanosoma brucei

描述（由申请方提供）：锥虫是一种寄生虫，可导致人类和牲畜衰弱，通常是致命性疾病。撒哈拉以南非洲的一个特别严重的问题是由布氏锥虫引起的，这是一种通过受感染的采采蝇叮咬传播的寄生虫。T.布氏杆菌通过在哺乳动物宿主的血液、组织空间以及最终的中枢神经系统中增殖而引起疾病。相关寄生虫对世界其他地区的人群同样重要，包括南美洲和中美洲，东南亚和中东。我们的长期目标是了解，在生化和遗传细节，协调锥虫基因表达的机制。为了实现这一目标，我们正在专门研究寄生虫用于调节其mRNA表达模式的机制。mRNA表达产生特征性和必需的蛋白质组，并决定寄生虫的代谢能力。作为理解mRNA表达控制的途径，我们正在制作T.布氏原轮寄生虫。我们目前还不知道其他类似的项目，但我们知道这种方法在酵母生物学研究和哺乳动物疾病探索中非常有用。我们提出的为期两年的项目是基于我们在体内UV交联蛋白质-RNA复合物和分析两种mRNA结合蛋白质的经验。拟议的项目将在目标1中建立RNA结合蛋白-mRNA蛋白质组，并在目标2中通过分析两种特定mRNA结合蛋白的mRNA靶点来提供数据集的实验验证。

DESCRIPTION (provided by applicant): Trypanosomatids are parasites that cause debilitating and often fatal diseases in humans and livestock. A particularly serious problem in sub-Saharan Africa is caused by Trypanosoma brucei, a parasite spread by the bite of an infected Tsetse fly. T. brucei causes disease by proliferating in the blood, tissue spaces, and eventually the central nervous system of its mammalian host. Related parasites are equally important to human populations in other parts of the world, including South and Central America, Southeastern Asia and the Middle East. Our long-term goal is to understand, in biochemical and genetic detail, the mechanisms that coordinate gene expression in trypanosomatids. To achieve this goal, we are specifically investigating the mechanism used by the parasites to regulate their mRNA expression pattern. mRNA expression gives rise to a characteristic and essential proteome and determines the metabolic capabilities of the parasites. As a pathway into understanding mRNA expression control, we are producing the mRNA-binding protein proteome for T. brucei procyclic parasites. We currently know of no other similar undertaking but are aware that this approach is extremely useful in the study of yeast biology and mammalian disease exploration. Our proposed two-year project is grounded in our experience in in vivo UV-crosslinking of protein-RNA complexes and analysis of two mRNA-binding proteins. The proposed project will establish the RNA-binding protein-mRNA proteome, in aim 1, and provide experimental verification of the dataset by analyzing the mRNA targets of two specific mRNA- binding proteins in aim 2.