Regulation of T Lymphocyte mRNA Degradation

描述(由申请人提供)：本研究职业生涯奖申请书描述了Paul R.Bohjanen博士的职业发展计划，以进一步发展他的研究计划，旨在了解信使核糖核酸降解在调节T淋巴细胞基因表达中的作用。Bohjanen博士最近完成了传染病临床培训，并于2000年7月开始担任助理教授，这是他的第一个教职。他提出的研究是基于这样一个假设，即信使核糖核酸的降解在调节T淋巴细胞基因表达方面起着重要作用。第一个特定的目标是确定在mRNA降解水平上受调控的T淋巴细胞基因。微阵列技术将被用来根据T淋巴细胞的mRNA衰减率来分析其表达的mRNA转录本，并识别其mRNA衰减率在细胞激活时发生变化的转录本。其衰变速度受到调控的特定的mRNA转录本将被进一步鉴定，以确定调节mRNA衰变的新的序列元件和反式作用因子。T淋巴细胞转录本的一个子集，包括细胞因子转录本和某些原癌基因转录本，包含被称为富含AU的元件(ARES)的序列，这些序列是mRNA降解的重要调节因素。HUA和TTP蛋白与ARE特异结合，从而调节mRNA的降解。第二个特殊目的是研究这些蛋白在T淋巴细胞中的表达和功能。明尼苏达大学为Bohjanen博士发展他的研究项目提供了一个强大和互动的智力环境。他与在T淋巴细胞免疫学、T淋巴细胞的病毒感染和RNA-蛋白质相互作用的生物化学等相关研究领域拥有专业知识的同事进行了大量的交流。他参加了免疫学中心、微生物学系和该大学的RNA生物学社区内的研究会议，将对他的实验室所做的工作进行持续的批判性评估。Bohjanen博士有足够的空间和资源来进行拟议的实验，而且通过生物医学基因组学中心可以使用设备来执行拟议的微阵列实验。独立科学家奖将为Bohjanen博士提供更多的研究支持和受保护的时间，使他能够建立一个富有成效的研究生涯。

DESCRIPTION (provided by applicant): This Research Career Award application describes a career development plan for Dr. Paul R. Bohjanen to further develop his research program directed toward understanding the role of mRNA degradation in regulating T lymphocyte gene expression. Dr. Bohjanen recently completed clinical training in infectious diseases and started his first faculty position as an Assistant Professor in July of 2000. His proposed research is based on the hypothesis that mRNA degradation plays an important role in regulating T lymphocyte gene expression. The first specific aim is to identify T lymphocyte genes that are regulated at the level of mRNA degradation. Microarray technology will be used to profile mRNA transcripts expressed in T lymphocytes based on their rates of mRNA decay and to identify transcripts whose rate of mRNA decay changes upon cellular activation. Specific mRNA transcripts whose rate of decay is regulated will be characterized further to identify novel sequence elements and trans-acting factors that regulate mRNA decay. A subset of T lymphocyte transcripts, including cytokine transcripts and certain proto-oncogene transcripts, contain sequences known as AU-rich elements (AREs) that are important regulators of mRNA degradation. The proteins HuA and TTP bind specifically to AREs and thereby regulate mRNA degradation. The second specific aim is to characterize the expression and function of these proteins in T lymphocytes. The University of Minnesota provides a strong and interactive intellectual environment for Dr. Bohjanen to develop his research program. He has numerous interactions with colleagues who have expertise in related research areas including T lymphocyte immunology, virus infection of T lymphocytes, and the biochemistry of RNA-protein interactions. His participation in research conferences within the Center for Immunology, Department of Microbiology, and the RNA biology community at the university will provide an ongoing critical evaluation of work performed in his laboratory. Dr. Bohjanen has adequate space and resources for carrying out the proposed experiments, and facilities are available through the Biomedical Genomics Center to perform the proposed microarray experiments. The Independent Scientist Award would provide Dr. Bohjanen with additional support and protected time for research to enable him to establish a productive research career.