Epigenetic Regulation of Drosophila Germline Development

摘要 研究：干细胞可以自我更新或分化成多种细胞类型。这些房产前景广阔 再生医学的治疗潜力。了解调节干细胞的分子机制 身份和维护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。表观遗传机制调控基因的动态变化 表达谱影响干细胞的自我更新和分化。我特别感兴趣 研究 Polycomb Group (PcG) 介导的干细胞表观遗传调控。我之前的工作 表征了在转变过程中调节 PcG 复合物（一种关键的表观遗传修饰剂）的新机制 从多能性到发育受限的细胞命运。目前，我正在研究PcG功能及其 果蝇卵巢种系中与 Piwi 的相互作用，受遗传、基因组、分子等因素影响 作为细胞生物学分析。 Piwi 是生殖干细胞的主要调节者。在辅导阶段，我会 表征 Piwi-PcG 相互作用并确定这种相互作用如何影响果蝇卵巢种系和 生殖干细胞。在独立阶段，我将描述 PcG 功能的分子效应 果蝇种系中 Piwi-PcG 相互作用。这项研究将对干细胞生物学产生重大影响， 表观遗传学，以及再生医学。 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。的 K99/R00 独立之路奖将使我获得实现我的长期目标所需的关键培训 术语研究和职业目标。我将使用从该提案中获得的实验数据作为我的基础 自己独立研究。 培训环境：林海帆博士（导师）、我的顾问委员会和耶鲁大学提供 优秀的培训计划、激发智力的社区以及支持良好的研究环境。 在这个培训环境中，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职的能力 教师职位并实现我的长期研究和职业目标。

ABSTRACT Research: 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 diseases, 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.