RUI-Investigating the Mechanism of GLO-1 Rab Function in C. Elegans Lysosome-related Organelle Biogenesis

智力优势：复杂生物体的细胞包含一系列不同的离散功能单位，称为细胞器。这些隔室执行基本的细胞活动，并在物种内和物种之间广泛保存。溶酶体是一种细胞器，存在于几乎所有的动植物细胞中，是主要的降解部位。有趣的是，在许多类型的细胞中，溶酶体相关细胞器(LRO)与传统的降解溶酶体共存，这是因为特定的途径参与了LRO的形成。然而，大多数已知的调节LRO形成的因素也在溶酶体的构建中发挥作用，这引发了什么控制LRO特定形成的问题。一个同源的Rab蛋白家族，通常作为开关来调节细胞器之间的物质转移过程，已经被发现在LRO的形成中发挥作用，而不是传统的溶酶体。本项目通过研究GLO-1 Rab蛋白的活性来探索这样的假设，即这些RAB控制LRO的特定形成过程，GLO-1 Rab蛋白在LRO的构建中起作用，称为肠道颗粒。肠道颗粒是在模式遗传有机体秀丽线虫的肠道细胞中发现的，类似于哺乳动物的细胞器，其功能是合成/储存调节色素沉着和血液凝固的物质。简而言之，这项研究将确定GLO-1功能的细胞位置，GLO-1活性的调节因素，以及GLO-1控制的过程。由于GLO-1高度保守，这项研究将为在不同的细胞和生物体中调节LRO形成的机制提供重要的见解。更广泛的影响：这项研究每年将有30名本科生参与合作、调查和原创研究。在PI研究实验室和高级细胞生物学课程(招生第24期)工作的本科生将设计、实施、解释和展示他们研究GLO-1在LRO形成中的作用的实验结果。该协会将参与HHMI和米勒基金会在刘易斯和克拉克学院支持的计划，通过指导当地高中和社区大学学生在研究实验室中关于LRO形成的研究，增加科学中代表性不足的群体的代表性。最终，这项工作将为大量和多样化的学生提供动手的科学培训，其中许多人将在研究和教育领域取得进展

Intellectual Merit: The cells of complex organisms contain a diverse array of discrete functional units called organelles. These compartments carry out essential cell activities and are broadly conserved within and between species. Lysosomes, one type of organelle found within nearly all plant and animal cells, function as major sites of degradation. Interestingly, in many cell types, lysosome-related organelles (LROs) co-exist with conventional degradative lysosomes due to the activity of specific pathways mediating the formation of LROs. However, most of the known factors that mediate LRO formation also function in the construction of lysosomes, raising the question of what controls the specific formation of LROs. A family of homologous Rab proteins, which generally act as switches to regulate the processes involved in moving material between organelles, have been identified that function in the formation of LROs but not conventional lysosomes. This project explores the hypothesis that these Rabs control LRO-specific formation processes by investigating the activity of the GLO-1 Rab protein that functions in the construction of an LRO called the gut granule. Gut granules are found within the intestinal cells of the model genetic organism C. elegans and are analogous to organelles in mammals that function in the synthesis/storage of substances mediating pigmentation and blood clotting. Briefly, the research will identify the cellular site of GLO-1 function, the regulators of GLO-1 activity, and the processes controlled by GLO-1. As GLO-1 is highly conserved, this research will provide important insights into the mechanisms mediating the formation of LROs in a diverse array of cells and organisms. Broader impacts: The research will involve 30 undergraduates a year in collaborative, investigative, and original research. Undergraduate students working in the PI's research laboratory and upper division Cell Biology course (enrollment 24) will design, implement, interpret, and present the results of their experiments investigating the function of GLO-1 in LRO formation. The PI will participate in HHMI and Miller Foundation supported initiatives at Lewis & Clark College to increase the representation of underrepresented groups in science by mentoring the studies of LRO formation by local high school and community college students in the research lab. Ultimately, this work will provide hands on scientific training for a large and diverse array of students, many of whom will progress on to careers in research and education