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CAREER: Investigation of the transcriptional networks that coordinate sperm morphogenesis

职业：研究协调精子形态发生的转录网络

基本信息

批准号：
1942922
负责人：
Jordan Ward
金额：
$ 120.73万
依托单位：
University of California-Santa Cruz
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-12-15 至 2024-11-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942922&HistoricalAwards=false
关键词：
CAREER Investigation transcriptional networks coordinate

项目摘要

Sperm are highly specialized types of cells which, along with eggs, are essential for passing genetic information down to the next generation. This project will use the nematode, C. elegans, in order to understand how genes are turned on and off to coordinate the complex cell development program leading to sperm formation. The research will be driven in large part by University of California-Santa Cruz undergraduate transfer students. UC Santa Cruz is a Hispanic-Serving Institution with a diverse student body. The institution enrolls a large number of junior transfer students, which is expected to increase due to a UC initiative to streamline the application process. The transfer student populations are diverse, comprising a large percentage of underrepresented minorities, and face significant challenges in STEM education and access to research experiences. This project will test a program to increase the retention and academic success of junior transfer students, involve them in research, create community, build identity, and help them navigate their journey to a UC Santa Cruz degree. Spermatogenesis involves a cascade of morphogenetic events. A single precursor cell must adopt and maintain a sperm fate, undergo reductive division, eliminate the vast majority of its cytoplasmic contents in the residual body, assemble and traffic organelles, and condense its chromatin. This project uses a combination of cutting-edge genome editing, drug-inducible protein depletion, and genomics to define the transcriptional networks that coordinate sperm morphogenesis. The research will investigate how the nuclear hormone receptor transcription factor NHR-23 controls meiotic division and organelle formation in spermatogenesis. It will test whether transcription factor inactivation is necessary for chromatin compaction and subsequent meiotic events in spermatogenesis. Genome editing and conditional protein depletion will be used to screen 20 uncharacterized transcription factors enriched in the spermatogenic germline for roles in spermatogenesis. Defining the gene regulatory networks underpinning spermatogenesis and defining key effectors is essential for developing formal models of sperm fate execution.This project is jointly funded by the Genetic Mechanisms cluster and the Cellular Dynamics and Function cluster in the Molecular and Cellular Biosciences DivisionThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

精子是一种高度特化的细胞，它与卵子沿着是将遗传信息传递给下一代所必需的。本课题将利用线虫C.为了了解基因是如何开启和关闭的，以协调导致精子形成的复杂细胞发育程序。这项研究将在很大程度上由加州大学圣克鲁斯分校的本科转学生推动。加州大学圣克鲁斯是一个西班牙裔服务机构与多元化的学生团体。该机构招收了大量的低年级转学生，由于UC简化申请流程的举措，预计这一人数将增加。转学生群体是多样化的，包括很大比例的代表性不足的少数民族，并面临着STEM教育和获得研究经验的重大挑战。该项目将测试一个计划，以提高低年级转学生的保留率和学业成功率，让他们参与研究，创建社区，建立身份，并帮助他们导航到加州大学圣克鲁斯学位的旅程。精子发生涉及一系列形态发生事件。单个前体细胞必须接受并维持精子的命运，经历还原性分裂，消除残留体内的绝大多数细胞质内容物，组装和运输细胞器，并浓缩其染色质。该项目结合了尖端的基因组编辑、药物诱导蛋白耗竭和基因组学来定义协调精子形态发生的转录网络。本研究将探讨核激素受体转录因子NHR-23在精子发生过程中如何调控减数分裂和细胞器的形成。它将测试转录因子失活是否是必要的染色质压实和随后的减数分裂事件在精子发生。将使用基因组编辑和条件性蛋白质耗竭来筛选在生精生殖系中富集的20种未表征的转录因子，以确定其在精子发生中的作用。定义支撑精子发生的基因调控网络和定义关键效应器对于开发精子命运执行的正式模型至关重要。该项目由分子和细胞生物科学部的遗传机制组和细胞动力学和功能组共同资助。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的评估来支持。影响审查标准。