Functional characters of microRNAs in T lymphocytes

T淋巴细胞中microRNA的功能特征

• 批准号: 6857667
• 负责人: MARIANTHI KIRIAKIDOU
• 金额: $ 9.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6857667
• 关键词: Retroviridae; T lymphocyte; apoptosis; bioinformatics; biotechnology; bone marrow; cell population study; cell proliferation; complementary RNA; flow cytometry; gene expression; green fluorescent proteins; hematopoietic stem cells; laboratory mouse; leukopoiesis; lymphopoiesis; messenger RNA; microRNAs; northern blottings; oligonucleotides; small interfering RNA; tissue /cell culture; transfection /expression vector

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.

描述（由申请人提供）：该提案的双重目标是研究 microRNA 在造血/T 细胞发育中的功能，并使申请人成为独立研究者。 MicroRNA 代表了一类新型的小调控 RNA。 miRNA 通过与其 mRNA 靶标中发现的 miRNA 识别元件进行碱基配对来控制基因表达。 miRNA在基因表达调控中的作用是多效性的，miRNA控制细胞增殖、凋亡和发育，尽管哺乳动物miRNA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尚不清楚。针对 miRNA 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 miRNA 功能的理解。在目标#1 中，将鉴定哺乳动物 miRNA 的 mRNA 靶标。提出了一种实验计算方法以及验证 miRNA 靶点的策略。在目标#2 中，将研究 miRNA 在小鼠造血/T 细胞发育中的功能。通过之前接受的类固醇生成分子生物学研究培训以及内科和风湿病学临床培训，申请人在过去几年中一直从事医师科学家的职业生涯。博士。 Warren Pear、Zissimos Mourelatos 和 Philip Cohen 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）领域的专业知识而受到认可，将赞助该候选人的科学发展。赞助机构的研究设施质量和可用资源的多样性，再加上赞助商的智力和学术实力，为拟议研究的开展提供了理想的环境。