Peroxisome biogenesis, dynamics, and degradation - Administrative Supplement

过氧化物酶体生物发生、动力学和降解 - 行政补充

• 批准号: 10614753
• 负责人: Bonnie Bartel
• 金额: $ 2.94万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10614753
• 关键词: Address; Administrative Supplement; Award; Biochemical; Biogenesis; Biological; Biology; Blindness; Cells; Chemicals; Childhood; Defect; Development; Disease; Eukaryota; Functional disorder; Genetic; Genetic Models; Grant; Growth; Health; Human Development; Impairment; Inherited; Knowledge; Life; Membrane; Metabolic; Modeling; Molecular; Mouse-ear Cress; Nerve Degeneration; Non-Insulin-Dependent Diabetes Mellitus; Organelles; Organism; Oxidative Stress; Parents; Plant Model; Plants; Process; Reaction; Regulation; Research; Scientist; Symptoms; Syndrome; System; Training; Ubiquitination; Yeasts; age related; experimental study; hearing impairment; improved; infancy; insight; live cell imaging; next generation; oxidative damage; peroxisome; plant growth/development; receptor recycling

Research Supplement to Promote Diversity in Health-Related Research Summary of parent award R35GM130338: Peroxisome Biogenesis, Dynamics, and Degradation Peroxisomes are eukaryotic organelles that are essential for life in plants and metazoans. Peroxisomes sequester various oxidative reactions, thereby improving metabolic efficiency while protecting cytosolic constituents from oxidative damage. Although our knowledge about peroxisome function and dysfunction is increasing, mechanistic understanding of how these critical organelles are formed, maintained, and turned over remains incomplete. The proposed studies aim to fill these gaps by answering the following questions: How do pre-peroxisomes originate? How do peroxisomal membrane complexities develop? How can chemical probes and genetic suppressors modulate peroxisome function? How are obsolete or damaged peroxisomes targeted for turnover? Does the ubiquitination machinery on the peroxisomal membrane moonlight in tasks beyond receptor recycling? These questions will be addressed using Arabidopsis thaliana; the peroxisomal functions, small size, and facile genetics of this model plant allow straightforward impairment and enhancement of peroxisomal processes in an intact multicellular organism. Moreover, the relatively large size of plant peroxisomes (compared to yeast and mammalian peroxisomes) offers unique opportunities to decipher peroxisome biogenesis and membrane intricacies using live-cell imaging. The proposed studies also will train the next generation of scientists in state-of-the-art genetic, biochemical, and cell biological approaches. Peroxisomal defects underlie the peroxisome biogenesis disorders, a group of inherited recessive syndromes that are generally fatal in infancy or childhood and are characterized by diverse symptoms including poor growth, multi-organ dysfunctions, hearing and vision loss, and psychomotor retardation. Peroxisome dysfunction also contributes to common age-related diseases (e.g., neurodegeneration, type 2 diabetes) that are exacerbated by oxidative stress. The proposed studies will exploit unique aspects of plant peroxisomes while taking advantage of knowledge from fungal and mammalian systems to provide insights that are likely to apply throughout eukaryotes. Continued development of evolutionarily distinct systems with unique advantages for elucidating peroxisome biology will advance hypotheses and mechanistic models to expand and refine our understanding of this essential organelle.

促进健康相关研究多样性的研究补编 母公司奖励摘要 R35 GM 130338：过氧化物酶体生物发生、动力学和降解 过氧化物酶体是植物和后生动物生命所必需的真核细胞器。 过氧化物酶体螯合各种氧化反应，从而提高代谢效率， 保护胞质成分免受氧化损伤。尽管我们对 过氧化物酶体功能和功能障碍正在增加，机械理解这些如何 关键细胞器的形成、维持和翻转仍然不完整。拟议 研究旨在通过回答以下问题来填补这些空白：前过氧化物酶体如何 起源？过氧化物酶体膜复杂性是如何形成的？化学探针和 遗传抑制因子调节过氧化物酶体功能？废弃或受损的过氧化物酶体 针对营业额？过氧化物酶体膜上的泛素化机制 除了受体回收外还兼职吗这些问题将使用 拟南芥;过氧化物酶体的功能，小尺寸，这种模式植物的遗传学 允许直接损害和增强过氧化物酶体过程在一个完整的 多细胞生物此外，植物过氧化物酶体的相对较大的尺寸（与 酵母和哺乳动物过氧化物酶体）提供了独特的机会来破译过氧化物酶体 生物发生和膜的复杂性使用活细胞成像。拟议的研究还将培训 下一代的科学家在国家的最先进的遗传，生物化学，细胞生物学 接近。 过氧化物酶体缺陷是过氧化物酶体生物合成障碍的基础， 隐性综合征，通常在婴儿期或儿童期致命，其特征是 多种症状，包括生长不良、多器官功能障碍、听力和视力丧失，以及 精神发育迟滞过氧化物酶体功能障碍也有助于常见的年龄相关性 疾病（例如，神经变性、2型糖尿病），其由氧化应激加剧。的 拟议的研究将利用植物过氧化物酶体的独特方面，同时利用 从真菌和哺乳动物系统的知识，以提供有可能适用的见解， 整个真核生物。进化上不同的系统的持续发展， 阐明过氧化物酶体生物学的优势将推进假说和机制模型 来扩展和完善我们对这个重要细胞器的理解。