Diet and Germline Progenitors

摘要/项目摘要 (来自家长助学金) 生物为了生存而进食，而饮食为生长和维持提供了物质。然而， 复杂的营养响应信号通路网络确保营养物质适当地 被分配和利用来支持细胞过程，如增殖和分化， 与发育阶段和生物体的需要相称。我们知道 响应饮食的信号是饮食成分功能供应的关键，因为 信号通路可以被操纵来克服营养不足，否则就会 损害了这些过程。然而，尽管饮食和新陈代谢的基本性质 信号，关键饮食因素的识别，它们如何触发特定的信号通路 活体，以及它们如何在机体新陈代谢中调节细胞行为的情况很差 明白了。我们正在使用线虫生殖系祖细胞作为模型来解决这一差距 系统。生殖细胞对饮食非常敏感，这使它们成为理想的模型。杆部和 祖细胞是基于饮食的信号的重要靶点，因为它们必须不断地 在不断变化的条件下维护组织和器官。线虫提供实验性服务 优势包括易于遗传和饮食操作。此外，线虫 实验室饮食--大肠杆菌--本身就是一种基因易驯化的有机体。使用互补的候选项 和不偏不倚的方法，这个项目将确定推动祖先的饮食成分 积累。饮食线索将与特定的已知(胰岛素、转化生长因子-β和TOR)或- 可能牵涉的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强劲积累如何影响父母的饮食 后代人。由于新陈代谢和营养的高度保守性- 在进化分化的生物体中发出反应信号，我们的研究将有助于 了解维持细胞增殖池的基本机制， 对人类的可能影响：生育、发育、退行性疾病、癌症、干细胞 细胞生物学和寄生虫生物学。

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.