Diet and Germline Progenitors

饮食和种系祖细胞

• 批准号: 10810328
• 负责人: E. Jane Albert Hubbard
• 金额: $ 1.66万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10810328
• 关键词: Address; Animals; Biological Models; Biology; Caenorhabditis elegans; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Complex; Cues; Degenerative Disorder; Development; Diet; Dietary Component; Dietary Factors; Eating; Ensure; Escherichia coli; Fertility; Generations; Germ Cells; Growth; Human; Impairment; Insulin; Internet; Laboratories; Link; Maintenance; Malignant Neoplasms; Metabolic; Metabolism; Modeling; Nature; Nutrient; Nutritional; Organ; Organism; Parasites; Process; Proliferating; Signal Pathway; Signal Transduction; Tissues; Transforming Growth Factor beta; cell behavior; dietary; dietary manipulation; genetic manipulation; in vivo; parent grant; progenitor; response; stem; stem cell biology; stem cells

Abstract/ Project Summary (from parent grant) Organisms eat to live, and diet provides material for growth and maintenance. However, complex webs of nutrient-responsive signaling pathways ensure that nutrients are properly allocated and utilized to support cellular processes such as proliferation and differentiation, commensurate with the demands of developmental stage and organismal needs. We know that signaling in response to diet is key to functional provisioning of dietary components, since signaling pathways can be manipulated to overcome nutritional deficits that would otherwise impair these processes. However, despite the fundamental nature of diet and metabolic signaling, the identity of key dietary factors, how they trigger particular signaling pathways in vivo, and how they operate within organismal metabolism to regulate cell behavior are poorly understood. We are addressing this gap using C. elegans germline progenitor cells as a model system. Germ cells are exquisitely sensitive to diet, making them an ideal model. Stem and progenitor cells are important targets of diet-based signaling, since they must continuously maintain tissues and organs under changing conditions. C. elegans offers experimental advantages including facile genetic and dietary manipulation. In addition, the C. elegans laboratory diet, E. coli, is itself a genetically tractable organism. Using complementary candidate and unbiased approaches, this project will identify dietary components that drive progenitor accumulation. Dietary cues will be linked to specific known (insulin, TGF-beta and TOR) or yet- to-be-implicated signaling pathways and cellular response mechanisms. The project will also address how robust accumulation of germline progenitors, in response to parental diet, impacts subsequent generations. Due to the highly conserved nature of metabolism and nutrient- reponsive signaling across evolutionarily divergent organisms, our studies will contribute to the understanding of fundamental mechanisms that maintain proliferating pools of cells, with possible implications in humans for fertility, development, degenerative diseases, cancer, stem cell biology, and parasite biology.

摘要/项目摘要 (from父母补助金） 生物体吃东西是为了生存，饮食提供生长和维持的物质。然而，在这方面， 复杂的营养反应信号通路网络确保了营养物质的适当 分配并用于支持细胞过程如增殖和分化， 与发育阶段的要求和生物体的需要相适应。我们知道 响应饮食的信号传导是饮食成分功能性供应的关键，因为 可以操纵信号通路来克服营养不足， 破坏这些过程。然而，尽管饮食和代谢的基本性质 信号，关键饮食因素的身份，它们如何触发特定的信号通路， 体内，以及它们如何在生物体代谢中调节细胞行为， 明白我们正在使用C来解决这个问题。线虫生殖系祖细胞作为模型 系统生殖细胞对饮食非常敏感，这使它们成为理想的模型。茎和 祖细胞是基于饮食的信号传导的重要靶点，因为它们必须持续地 在变化的条件下维持组织和器官。C. elegans提供了实验性的 这些优势包括基因和饮食控制。此外，C. elegans 实验室饮食、E.大肠杆菌本身是一种遗传上易处理的生物体。使用互补候选人 和公正的方法，该项目将确定饮食成分，驱动祖细胞 积累饮食提示将与特定的已知（胰岛素，TGF-β和TOR）或尚未- 信号通路和细胞反应机制。该项目还将 解决生殖系祖细胞的大量积累如何响应亲本饮食， 后代。由于新陈代谢和营养的高度保守性- 响应信号在进化上不同的生物体，我们的研究将有助于 了解维持细胞增殖池的基本机制， 对人类生育力、发育、退行性疾病、癌症、干细胞的可能影响 细胞生物学和寄生虫生物学。