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被称为细胞器的离散功能单元。这些区室进行基本的细胞活动，在物种内部和物种之间广泛保守。溶酶体是几乎在所有植物和动物细胞中发现的一种细胞器，是降解的主要场所。有趣的是，在许多细胞类型中，由于介导LROs形成的特定途径的活性，溶酶体相关细胞器（LROs）与常规降解溶酶体共存。然而，大多数介导LRO形成的已知因子也在溶酶体的构建中起作用，这就提出了什么控制LRO的特定形成的问题。同源Rab蛋白家族通常作为调节细胞器之间移动物质过程的开关，已被确定在LROs的形成中起作用，而不是传统的溶酶体。该项目通过研究GLO-1 Rab蛋白的活性，探讨了这些Rabs控制LRO特异性形成过程的假设，该蛋白在构建称为肠道颗粒的LRO中起作用。肠道颗粒存在于模式遗传生物秀丽隐杆线虫的肠细胞中，类似于哺乳动物的细胞器，在合成/储存介导色素沉着和血液凝固的物质中起作用。简而言之，本研究将确定glo1功能的细胞位点，glo1活性的调节因子以及glo1控制的过程。由于GLO-1是高度保守的，这项研究将为多种细胞和生物体中介导LROs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（第24届学员）工作的本科生将设计、实施、解释并展示他们研究GLO-1在LRO形成中的功能的实验结果。PI将参与HHMI和米勒基金会支持的Lewis & Clark学院倡议，通过指导当地高中和社区大学学生在研究实验室中对LRO形成的研究，增加科学界代表性不足群体的代表性。最终，这项工作将为大量不同类型的学生提供实际的科学培训，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