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，并将申请人确立为独立研究者。MicroRNA代表一类新型的小调节RNA。miRNAs通过与其mRNA靶中发现的miRNAs识别元件进行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性的，miRNAs控制细胞的增殖、凋亡和发育，尽管哺乳动物miRNAs调控的许多基因尚不清楚。miRNA在T淋巴细胞及其发育中的作用完全未知。针对miRNAs在造血/T细胞发育中的功能的研究有望揭示控制造血/淋巴细胞发育的新途径，同时增强我们对miRNAs功能的理解。在目标#1中，将鉴定哺乳动物miRNA的mRNA靶标。沿着提出了一种实验-计算方法，并提供了验证miRNA靶点的策略。在目标#2中，将研究miRNA在鼠造血/T细胞发育中的功能。申请人在过去的几年里一直从事医生科学家的职业生涯，通过她先前在类固醇生成分子生物学方面的研究培训以及内科和流变学方面的临床培训。Warren Pear、Zissimos Mourelatos和Philip Cohen博士因其在T细胞发育和免疫学（Pear和Cohen博士）以及microRNA生物学（Mourelatos博士）领域的专业知识而获得认可，他们将赞助候选人的科学发展。研究设施的质量和赞助机构可用资源的多样性，再加上赞助商的智力和学术实力，为开展拟议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.