Coordination of metabolic and signal transduction pathways

在发育过程中，细胞分裂、分化并组织成专门的组织和器官。这些过程需要细胞构建块，这些构建块由代谢途径使用饮食中提供的前体产生。当营养缺乏或代谢障碍时，细胞必须适应以优化营养的使用，优先安排某些细胞功能，并调整其他功能以应对关键代谢物的可获得性。出于这些原因，细胞必须将代谢信息传递给调节生长和发育的细胞信号通路。传递这一信息所涉及的机制还不完全清楚。*我们的研究计划试图了解代谢不足和失衡是如何传递到复杂的多细胞有机体中调节生长和发育的系统的。我们使用线虫线虫进行这些分析，因为它有不变的发育程序；动物总是有相同数量的细胞，它们的发育时间具有高度的重复性，很容易识别发育阶段。这些动物作为一个实用的系统来研究和识别由于代谢或信号蛋白的扰动而导致的发育影响。*我们提议的计划将：1)识别影响发育的代谢失衡；2)识别和描述感知和响应这些代谢失衡的细胞信号通路；3)确定一个组织中的代谢失调如何影响其他组织。这些分析将提高我们对代谢功能障碍影响发育的基本生物学机制的理解。从线虫到人类的代谢途径是高度保守的，因此我们在线虫中发现的分子事件很可能在其他生物中发生。**

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. **