RUI: Genetic and Molecular Analysis of Lysosome Assembly and Stability in C. Elegans

溶酶体是普遍存在的细胞隔室，在细胞成分的降解和周转中起着很好的作用。溶酶体在多种重要的细胞过程中发挥作用，包括向免疫系统提供抗原，细胞表面信号分子的周转，组织重塑和病原体的破坏。虽然对溶酶体的细胞和生化功能了解很多，但对多细胞动物中溶酶体组装和维持的过程仍然知之甚少。为了帮助理解这些过程，Hermann实验室已经开始鉴定模型多细胞生物秀丽隐杆线虫肠细胞中溶酶体组装/稳定性所必需的基因。其中鉴定出的基因之一glo1编码一种可能调节细胞间转运的Rab GTPase。这项工作旨在确定glo1是否在溶酶体的组装或维持中起作用，以及glo1是否阻止溶酶体与细胞膜的不适当融合。为了了解溶酶体组装/稳定性的哪一步需要glo1蛋白的功能，本研究将确定glo1的亚细胞定位。最后，该项目将扩展导致鉴定glo1的试点基因筛选，以鉴定溶酶体组装/维持所必需的其他基因。本研究将鉴定和描述在所有多细胞动物中可能在溶酶体的组装/维持中起作用的基因的活性。调节溶酶体的含量可以有效地防止细胞中功能失调的蛋白质和细胞器的积累。该项目正在一所本科院校进行，大量本科生将接受研究方面的培训，作为其正式课程作业和独立研究项目的一部分。

Lysosomes are ubiquitous cellular compartments with well-characterized roles in the degradation and turnover of cellular components. Lysosomes function in a diverse array of important cellular processes including the presentation of antigens to the immune system, the turnover of cell surface signaling molecules, tissue remodeling, and the destruction of pathogens. While much is known regarding the cellular and biochemical function of lysosomes, the processes involved in lysosome assembly and maintenance in multicellular animals remain poorly understood. To aid in the understanding of these processes, the Hermann lab has begun to identify genes necessary for the assembly/stability of lysosomes in the intestinal cells of the model multicellular organism, C. elegans. One of the genes identified, glo-1, encodes a Rab GTPase that may regulate transport between cellular compartments. This work aims to determine whether glo-1 functions in the assembly or the maintenance of lysosomes and if glo-1 prevents the inappropriate fusion of lysosomes with the cell membrane. To learn which step in lysosome assembly/stability requires GLO-1 protein function, this research will determine the sub-cellular localization of GLO-1. Finally, this project will extend the pilot genetic screen that led to the identification of glo-1 to identify additional genes that are necessary for lysosome assembly/maintenance. This research will identify and characterize the activity of genes that are likely to function in the assembly/maintenance of lysosomes in all multicellular animals. Regulation of lysosome content effectively prevents the accumulation of dysfunctional proteins and organelles in cells. The project is being conducted at an undergraduate insitution, and large numbers of undergraduate students will receive training in research as part of their formal course work and in independent research projects.