在适应饥饿或营养缺陷条件时，溶酶体作为信号中心和细胞消化站对维持细胞稳态和生存起了关键作用。目前对于溶酶体是如何应答饥饿刺激以及溶酶体自身形态和功能是如何被调控还缺乏深入了解。借助模式生物秀丽线虫，可以实现在动物个体水平上对溶酶体应答饥饿刺激的调控研究。我们的前期工作显示，在饥饿条件下线虫溶酶体形态发生剧烈变化，形成高度动态的管状结构，且降解活性显著增强。本课题将研究饥饿条件下溶酶体运输、小G蛋白、Ca2+外流、mTOR信号、细胞自噬等对溶酶体管状形变的调控，阐明管状溶酶体的形成和维持机制，并进一步探讨溶酶体管状形变对细胞应答饥饿刺激的生理意义，加深对溶酶体形态功能调控的理解，为溶酶体功能异常相关疾病的治疗提供科学依据。

As the signaling hubs and degradation stations, lysosomes are critical for maintaining cellular homeostasis and survival in adaption to starvation or nutrient deprivation. However, much less is understood about how lysosomes respond to starvation stress and how the lysosomal morphology and function are regulated. Working on C. elegans makes it possible to study the regulations of lysosomes in response to starvation at the animal level. Our preliminary works found that the nematode lysosomal morphology changes drastically to form highly dynamic tubules and the lysosomal degradation activity is significantly enhanced upon starvation. To better understand how the tubular lysosomes are formed and maintained and further investigate the physiological significance of the lysosomal tubulation in response to starvation, we propose to analyze the detail effects of the lysosomal transport, small GTPases, Ca2+ efflux, mTOR signaling and autophagy on lysosomal tabulation upon starvation. Our proposed studies are expected to explore the regulation mechanisms of lysosomal morphology and function, and provide scientific strategies for the treatment of multiple diseases related to lysosomal dysfunction.