Epigenetic Regulation of Drosophila Germline Development

果蝇种系发育的表观遗传调控

• 批准号: 8370300
• 负责人: Jamy C. Peng
• 金额: $ 11.44万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8370300
• 关键词: Adult; Advisory Committees; Affect; Amino Acids; Award; Binding; Biogenesis; Biological; Biological Models; Cell Maintenance; Cells; Communities; Complex; DNA; Data; Defect; Development; Disease; Drosophila genus; Elements; Environment; Epigenetic Process; Exhibits; Faculty; Failure; Foundations; Future; Gene Expression; Gene Targeting; Genetic; Genomic Instability; Genomics; Goals; Grant; Health; Histone H3; Human; Human body; In Vitro; Knowledge; Lead; Leadership; Link; Lysine; Maintenance; Mediating; Mediator of activation protein; Mentors; Molecular; Molecular Profiling; Mutation; Occupations; Ovarian; Ovarian Tissue; PRC1 Protein; Pathway interactions; Phase; Polycomb; Positioning Attribute; Production; Property; Proteins; RNA Polymerase II; Regenerative Medicine; Regulation; Reproductive Biology; Research; Research Support; Scientist; Site; Stem cells; Tertiary Protein Structure; Testing; Therapeutic; Tissues; Training; Training Programs; Universities; Work; Writing; base; career; cell type; genome-wide; in vivo; interest; mature animal; neuronal cell body; novel; piRNA; pluripotency; programs; self-renewal; skills; stem cell biology; stem cell division

DESCRIPTION (provided by applicant): Stem cells can self-renew or differentiate into multiple cell types. These properties promise great therapeutic potentials in regenerative medicine. Understanding the molecular mechanisms regulating stem cell identity and maintenance will provide fundamental knowledge about human health and likely accelerate the use of stem cells in regenerative medicine. Epigenetic mechanisms regulate dynamic changes of gene expression profiles to influence stem cell self-renewal and differentiation. I am especially interested in investigating Polycomb Group (PcG)-mediated epigenetic regulation of stem cells. My previous work characterized a novel mechanism regulating a PcG complex, a key epigenetic modifier, during the transition from pluripotency to developmentally restricted cell fates. Currently, I am investigating PcG functions and their interaction with Piwi in Drosophila ovarian germline, which is tractable to genetic, genomic, molecular, as well as cell biological analyses. Piwi is a master regulator of germline stem cells. During the mentored phase, I will characterize Piwi-PcG interaction and determine how this interaction impacts Drosophila ovarian germline and germline stem cells. During the independent phase, I will characterize the molecular effects of PcG functions and Piwi-PcG interaction in Drosophila germline. This study will have significant impact on stem cell biology, epigenetics, as well as regenerative medicine. Candidate: My long-term research goal is to investigate how epigenetic mechanisms impact human health and disease, specifically to understand how epigenetic mechanisms regulate complex tissues. My long-term career goals are to maintain a successful independent research program and educate future scientists. The K99/R00 Pathway to Independence Award will allow me to gain the critical training needed to achieve my long-term research and career goals. I will use experimental data obtained from this proposal as the basis for my own independent research. Training environment: Dr. Haifan Lin (mentor), my advisory committee, and Yale University provide an excellent training program, an intellectually stimulating community, and a well-supported research environment. In this training environment I will gain scientific knowledge, research expertise, grant writing ability, lab management skill, and additional leadership skills. All these will enhance my ability to obtain a tenure-track faculty position and achieve my long-term research and career goals. PUBLIC HEALTH RELEVANCE: The self-renewal and differentiability of stem cells promise great therapeutic potentials in regenerative medicine. This proposal aims to understand the mechanisms regulating gene expression that program stem cell identity by using Drosophila as the model system. This work would reveal fundamental knowledge about stem cell biology, thereby accelerating the use of stem cells in regenerative medicine.

描述（申请人提供）：干细胞可以自我更新或分化成多种细胞类型。这些特性有望在再生医学中发挥巨大的治疗潜力。了解调节干细胞身份和维持的分子机制将提供有关人类健康的基础知识，并可能加速干细胞在再生医学中的应用。表观遗传机制调节基因表达谱的动态变化，从而影响干细胞的自我更新和分化。我对研究 Polycomb Group (PcG) 介导的干细胞表观遗传调控特别感兴趣。我之前的工作描述了在从多能性到发育受限细胞命运的转变过程中调节 PcG 复合物（一种关键的表观遗传修饰剂）的新机制。目前，我正在研究果蝇卵巢种系中 PcG 的功能及其与 Piwi 的相互作用，这易于进行遗传、基因组、分子以及细胞生物学分析。 Piwi 是生殖干细胞的主要调节者。在指导阶段，我将描述 Piwi-PcG 相互作用的特征，并确定这种相互作用如何影响果蝇卵巢生殖系和生殖系干细胞。在独立阶段，我将描述果蝇种系中 PcG 功能和 Piwi-PcG 相互作用的分子效应。这项研究将对干细胞生物学、表观遗传学以及再生医学产生重大影响。候选人：我的长期研究目标是研究表观遗传机制如何影响人类健康和疾病，特别是了解表观遗传机制如何调节复杂组织。我的长期职业目标是维持成功的独立研究计划并教育未来的科学家。 K99/R00 独立之路奖将使我获得实现长期研究和职业目标所需的关键培训。我将使用从该提案中获得的实验数据作为我自己独立研究的基础。培训环境：我的顾问委员会林海帆博士（导师）和耶鲁大学提供了出色的培训计划、激发智力的社区以及支持良好的研究环境。在这种培训环境中，我将获得科学知识、研究专业知识、资助写作能力、实验室管理技能和其他领导技能。所有这些都将增强我获得终身教授职位并实现我的长期研究和职业目标的能力。 公共健康相关性：干细胞的自我更新和分化能力在再生医学领域具有巨大的治疗潜力。该提案旨在通过使用果蝇作为模型系统来了解调节干细胞身份的基因表达的机制。这项工作将揭示干细胞生物学的基础知识，从而加速干细胞在再生医学中的应用。