Extreme cell growth in support of stem cell proliferation and niche exit

极端的细胞生长支持干细胞增殖和利基退出

• 批准号: 10756338
• 负责人: Kacy Lynn Gordon
• 金额: $ 2.67万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756338
• 关键词: Adult; Affect; Animals; Biological Assay; Caenorhabditis elegans; Chromatin; Data; Defect; Development; Diapause; Fertility; Future; Genes; Genetic; Genetic Models; Gonadal structure; Growth and Development function; Image; Life; Morphology; Mutagenicity Tests; Nematoda; Pathway interactions; Population; Recovery; Regulation; Regulator Genes; Reproduction; Reproductive system; Research; Role; Scientist; Stress; Stressful Event; Systems Biology; Systems Development; Technical Expertise; Technology; Training; Transcriptional Regulation; Work; career; cell growth; gene discovery; improved; model organism; reproductive; reproductive development; response; screening; stem cell proliferation; stress state; transcriptome sequencing; transcriptomics; virtual

Introduction: The nematode C. elegans has the ability to reversibly halt its development in response to adverse environmental conditions that make reproduction unfavorable. Two of the most well known diapause states are “dauer diapause,” a response to early life stressful conditions, and “adult reproductive diapause” (ARD), resulting from experiencing stressful conditions later in development. While there has been previous work on reproductive system development in dauer and ARD, less is known about its recovery. We propose a project in which the genetic mechanisms of recovery from each state are elucidated, culminating in a comparison between genetic recovery from two different stress-states. Aim 1: Characterize morphologic and gene regulatory changes during gonad recovery Aim 1A) We will use live imaging to illuminate common defects in recovery from both dauer and ARD; this will provide clues to the genetic pathways affected by, and necessary for, recovery. Aim 1B) We will utilize RNAseq technology to determine differentially regulated genes in the recovery from ARD; this will help elucidate genes implicated in ARD developmental recovery. Aim 2: Identify genetic regulators of reproductive recovery from dauer and ARD Aim 2A) We will perform a mutagen screen to discover genes that seem to serve specifically in recovery from dauer and/or ARD, and are not implicated in continuous reproductive development in non-stressful conditions (i.e. those that have post-diapause defects in reproductive development but the same defects are not seen in a continuously fed population.) Aim 2B) We will utilize a candidate approach to identifying genes important to dauer and/or ARD recovery through virtually screening existing transcriptomics data, enriching for differentially regulated genes known to function in the development of the reproductive system. Aim 3: Understand the role of chromatin regulation in diapause and reversal We will examine the role of broad transcriptional regulation through live imaging and assaying chromatin compaction in the germline. Training Plan: The proposed training plan will not only allow me to gain the technical skills necessary to answer these interesting questions, but will also provide me with many opportunities to improve upon my weaknesses as a scientist, such as opportunities for publicly presenting my research. Additionally, the proposed training plan will give me the necessary coursework to pivot towards a more Systems Biology oriented career in the future.

线虫C. elegans具有可逆地停止其发育的能力