Coordination of metabolic and signal transduction pathways

代谢和信号转导途径的协调

• 批准号: RGPIN-2016-06339
• 负责人: Macneil, Lesley
• 金额: $ 3.13万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688606
• 关键词: Coordination; metabolic; signal; transduction; pathways

During development cells divide, differentiate, and organize themselves into specialized tissues and organs. These processes require cellular building blocks that are produced by metabolic pathways using precursors supplied in the diet. When nutrients are lacking, or when there is metabolic dysfunction, cells must adapt to optimize the use of nutrients, prioritize certain cellular functions and adjust others to cope with the availability of critical metabolites. For these reasons, cells must convey metabolic information to the cellular signaling pathways that regulate growth and development. The mechanisms involved in conveying this information are not completely understood. ***Our research program seeks to understand how metabolic insufficiencies and imbalances are communicated to the systems that regulate growth and development in a complex, multi-cellular organism. We are using the nematode worm C. elegans for these analyses because it has invariant developmental program; animals always have the same number of cells, their developmental timing is highly reproducible and developmental stages can easily be identified. These animals serve as a practical system to study and identify developmental effects resulting from the perturbation of metabolic or signaling proteins. ***Our proposed program will: 1) identify metabolic imbalances that influence development 2) identify and characterize cellular signaling pathways that sense and respond to these metabolic imbalances 3) determine how metabolic dysfunction in one tissue affects other tissues. These analyses will improve our understanding of the basic biological mechanisms through which metabolic dysfunction mediates effects on development. Metabolic pathways from C. elegans to humans are highly conserved and therefore molecular events that we uncover in C. elegans are likely to occur in other organisms. **

在发育过程中，细胞分裂、分化并组织成专门的组织和器官。这些过程需要通过代谢途径使用饮食中提供的前体产生的细胞构建块。当营养素缺乏时，或者当存在代谢功能障碍时，细胞必须适应以优化营养素的使用，优先考虑某些细胞功能，并调整其他功能以科普关键代谢物的可用性。由于这些原因，细胞必须将代谢信息传递给调节生长和发育的细胞信号传导途径。传递这一信息的机制尚未完全了解。* 我们的研究计划旨在了解代谢的不平衡和不平衡是如何传达到调节复杂的多细胞生物体生长和发育的系统的。我们用的是线虫C。因为它具有不变的发育程序;动物总是具有相同数量的细胞，它们的发育时间是高度可重复的，并且发育阶段可以很容易地被识别。这些动物作为一个实用的系统来研究和识别由代谢或信号蛋白的扰动引起的发育影响。* 我们提出的计划将：1）识别影响发育的代谢失衡2）识别和表征感知和响应这些代谢失衡的细胞信号通路3）确定一种组织中的代谢功能障碍如何影响其他组织。这些分析将提高我们对代谢功能障碍介导对发育影响的基本生物学机制的理解。C.的代谢途径。从秀丽隐杆线虫到人类都是高度保守的，因此我们在C.线虫很可能存在于其他生物体中。**