Functional characters of microRNAs in T lymphocytes

描述（由申请人提供）：本提案的双重目标是研究microrna在造血/T细胞发育中的功能，并确立申请人作为独立研究者的地位。MicroRNAs是一类新型的小调控rna。mirna通过与在其mRNA靶标中发现的mirna识别元件碱基配对来控制基因表达。miRNAs在基因表达调控中的作用是多效的，尽管哺乳动物miRNAs调控的许多基因尚不清楚，但miRNAs控制细胞增殖、凋亡和发育。mirna在T淋巴细胞及其发育中的作用是完全未知的。研究mirna在造血/T细胞发育中的功能有望揭示控制造血/淋巴细胞发育的新途径，同时增强我们对mirna功能的理解。在Aim #1中，将鉴定哺乳动物mirna的mRNA靶点。提出了一种实验计算方法以及验证miRNA靶标的策略。在Aim #2中，将研究mirna在小鼠造血/T细胞发育中的功能。申请人在过去的几年里，通过类固醇分子生物学的研究培训以及内科和风湿病学的临床培训，作为一名内科科学家。Drs。Warren Pear， Zissimos Mourelatos和Philip Cohen，以其在T细胞发育和免疫学领域的专业知识而闻名。Pear和Cohen)和microRNA生物学（Mourelatos博士）将资助候选人的科学发展。资助院校的研究设施质素优良，资源丰富，再加上资助机构的智力和学术实力，为进行拟议的研究提供了理想的环境。

DESCRIPTION (provided by applicant): The dual goals of this proposal are to investigate the function of microRNAs in hematopoietic/T cell development and to establish the applicant as an independent investigator. MicroRNAs represent a novel class of small regulatory RNAs. miRNAs control gene expression by base pairing with miRNA-recognition elements found in their mRNA targets. The effects of miRNAs in gene expression regulation are pleiotropic, miRNAs control cellular proliferation, apoptosis and development, although many of the genes that mammalian miRNAs regulate are unknown. The role of miRNAs in T lymphocytes and their development is completely unknown. Studies to address the function of miRNAs in hematopoietic/T cell development promise to unravel novel pathways that control hematopoietic/lymphocytic development and at the same time enhance our understanding of the function of miRNAs. In Aim #1, mRNA targets for mammalian miRNAs will be identified. An experimental-computational approach is presented along with strategies for validation of miRNA targets. In Aim #2, the function of miRNAs in murine hematopoietic/T cell development will be investigated. The applicant has spent the last several years for a career as a physician-scientist, through her prior research training in the molecular biology of steroidogenesis and clinical training in Internal Medicine and Rheumatology. Drs. Warren Pear, Zissimos Mourelatos and Philip Cohen, recognized for their expertise in the fields of T cell development and Immunology (Drs. Pear and Cohen) and microRNA biology (Dr. Mourelatos), will sponsor the candidate's scientific development. The quality of the research facilities and the diversity of the resources available at the Sponsoring Institution in combination with the intellectual and academic strength of the sponsors, provide an ideal setting for the conduction of the proposed studies.