mRNA-binding proteome in Trypanosoma brucei

布氏锥虫中的 mRNA 结合蛋白质组

基本信息

批准号：
8689279
负责人：
Vivian Bellofatto
金额：
$ 23.85万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689279
关键词：
3&apos Untranslated Regions Africa South of the Sahara African Animal Model Antibodies Arthropods Binding Binding Proteins Biochemical Biochemical Genetics Biological Biology Bite Blood Carbon Cell Cycle Progression Cell Differentiation process Cell Line Cells Central America Cessation of life Characteristics Code Complement Complex Coupled Data Set Development Disease Drug Targeting Environment Epitopes Foundations Gene Expression Gene Expression Profile Gene Expression Regulation Genetic Genetic Translation Genomics Goals Health High-Throughput Nucleotide Sequencing Human Immunoprecipitation Individual Infection Insect Vectors Label Leishmania Length Libraries Life Cycle Stages Livestock Measures Membrane Messenger RNA Metabolic Metabolic Pathway Metabolism Middle East Neuraxis Open Reading Frames Organism Parasites Parasitic infection Pathway interactions Pattern Play Polyribosomes Population Process Proliferating Protein Binding Proteins Proteome Pyroxylin RNA RNA Recognition Motif RNA-Binding Proteins RNA-Protein Interaction Role Scanning Seminal Serum Sodium Dodecyl Sulfate-PAGE South America Southeastern Asia Staging System Technology Testing Tissues Transcriptional Regulation Transgenic Organisms Translating Trypanosoma Trypanosoma brucei brucei Tsetse Flies Untranslated Regions Yeasts burden of illness crosslink disability-adjusted life years experience in vivo insight mRNA Expression mRNA Stability next generation sequencing novel programs protein crosslink public health relevance research study response

项目摘要

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.

描述（由申请人提供）：锥虫是一种寄生虫，会导致人类和牲畜衰弱甚至致命的疾病。撒哈拉以南非洲地区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。布氏锥虫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类同样重要，包括南美洲和中美洲、东南亚和中东。我们的长期目标是从生化和遗传细节上了解锥虫动物基因表达的协调机制。为了实现这一目标，我们正在专门研究寄生虫调节其 mRNA 表达模式的机制。 mRNA 表达产生特征性的必需蛋白质组，并决定寄生虫的代谢能力。作为了解 mRNA 表达控制的途径，我们正在生产布氏锥虫原循环寄生虫的 mRNA 结合蛋白蛋白质组。目前我们不知道还有其他类似的工作，但我们知道这种方法在酵母生物学和哺乳动物疾病探索的研究中非常有用。我们提出的为期两年的项目基于我们在体内蛋白质-RNA 复合物紫外交联和两种 mRNA 结合蛋白分析方面的经验。拟议项目将在目标 1 中建立 RNA 结合蛋白-mRNA 蛋白质组，并通过分析目标 2 中两种特定 mRNA 结合蛋白的 mRNA 靶标来提供数据集的实验验证。