Epigenetic Regulation of Drosophila Germline Development

摘要 研究：干细胞可以自我更新或分化为多种细胞类型。这些物业前景看好。 再生医学的治疗潜力。了解干细胞调控的分子机制 身份和维护将提供有关人类健康的基本知识，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的动态变化 表达谱对干细胞自我更新和分化的影响。我特别感兴趣的是 研究聚梳组(PcG)介导的干细胞表观遗传调控。我以前的作品 描述了在转换过程中调节PcG复合体的新机制，PcG复合体是关键的表观遗传修饰物 从多能性到发育受限的细胞命运。目前，我正在研究PcG函数及其 在果蝇卵巢生殖系中与Piwi的相互作用，这对遗传、基因组和分子都是易感的 作为细胞生物学分析。Piwi是生殖系干细胞的主要调节者。在指导阶段，我将 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生殖系和 生殖系干细胞。在独立阶段，我将描述PcG功能的分子效应 以及Piwi-PcG在果蝇种系中的相互作用。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，特别是为了了解表观遗传机制如何调节复杂的组织。我的长期生活 职业目标是保持一个成功的独立研究计划，并培养未来的科学家。这个 K99/R00独立之路奖将使我获得必要的关键培训，以实现我的长期- 学期研究和职业目标。我将使用从这项提案中获得的实验数据作为我的 自己的独立研究。 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，以及得到良好支持的研究环境。 在这个培训环境中，我将获得科学知识、研究专长、写作能力、实验室 管理技能，以及额外的领导技能。所有这些都将提高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.