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

RUI-研究线虫溶酶体相关细胞器生物发生中 GLO-1 Rab 功能的机制

• 批准号: 1120835
• 负责人: Greg Hermann
• 金额: $ 41.33万
• 依托单位: Lewis and Clark College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1120835&HistoricalAwards=false
• 关键词: RUI; Investigating; Mechanism; GLO; Rab

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

智力优点：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。 这些区室进行基本的细胞活动，并在物种内和物种之间广泛保守。 溶酶体是几乎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LRO形成的特定途径的活性，溶酶体相关细胞器（LRO）与常规降解溶酶体共存。 然而，大多数已知的介导LRO形成的因子也在溶酶体的构建中起作用，这就提出了是什么控制LRO的特异性形成的问题。 同源Rab蛋白家族通常作为开关来调节参与细胞器之间物质移动的过程，已被鉴定在LRO而不是常规溶酶体的形成中起作用。 该项目探讨了这一假设，即这些Rabs通过研究GLO-1 Rab蛋白的活性来控制LRO特异性形成过程，该蛋白在称为肠道颗粒的LRO的构建中发挥作用。 在模型遗传生物体C的肠细胞内发现肠颗粒。线虫，并且类似于哺乳动物中的细胞器，其在介导色素沉着和血液凝固的物质的合成/储存中起作用。 简而言之，这项研究将确定GLO-1功能的细胞位点，GLO-1活性的调节剂以及GLO-1控制的过程。 由于GLO-1是高度保守的，这项研究将提供重要的见解，介导的机制，形成LRO在各种各样的细胞和生物体。更广泛的影响：这项研究将涉及30名本科生每年在合作，调查和原创性研究。 在PI研究实验室和高年级细胞生物学课程（招生24名）工作的本科生将设计、实施、解释和展示他们研究GLO-1在LRO形成中的功能的实验结果。 PI将参与HHMI和米勒基金会支持的刘易斯克拉克学院的倡议，通过指导当地高中和社区大学学生在研究实验室中进行的LRO形成研究，增加科学领域代表性不足群体的代表性。 最终，这项工作将为大量不同的学生提供科学培训，其中许多人将在研究和教育事业中取得进展