Peroxisomal impacts on cellular quality control

过氧化物酶体对细胞质量控制的影响

• 批准号: 10613572
• 负责人: DurreShahwar Muhammad
• 金额: $ 18.17万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10613572
• 关键词: Academy; Address; Affect; Antioxidants; Arabidopsis; Autophagocytosis; Bacteria; Biochemistry; Biogenesis; Biological Assay; Caenorhabditis elegans; Cataloging; Cell Nucleus; Cells; Cellular biology; Communication; Complement; Computational Biology; Cytosol; Data; Defect; Development; Disease; Environment; Equipment; Etiology; Eukaryota; Experimental Designs; Exposure to; Fostering; Functional disorder; Genes; Genetic Transcription; Goals; Health; Homeostasis; Hormones; Housing; Human; Impairment; Institution; Knowledge; Mammals; Mass Spectrum Analysis; Mediating; Medical center; Membrane Proteins; Mentors; Metabolic; MicroRNAs; Modeling; Molecular Chaperones; Organelles; Pathway interactions; Patients; Peptide Hydrolases; Phosphotransferases; Physiological; Plant Growth Regulators; Plants; Positioning Attribute; Protein Import; Protein Isoforms; Proteins; Proteomics; Publications; Quality Control; RNA Sequences; Reaction; Reactive Oxygen Species; Readiness; Research; Rice; Scientist; Signal Pathway; Signal Transduction; Surveys; System; Systems Biology; Texas; Training; Transcript; Universities; Yeasts; antioxidant enzyme; career; catalase; comparative; design; endopeptidase La; experience; experimental study; farmer; insight; inter-institutional; job market; knock-down; lipid metabolism; live cell imaging; mutant; next generation; overexpression; oxidation; pedagogy; peroxisome; peroxisome membrane; post-doctoral training; posttranscriptional; predictive modeling; prevent; professor; response; stem; supportive environment; transcription factor; transcriptome; transcriptomics

PROJECT SUMMARY – Peroxisomal impacts on cellular quality control Career Goals: The candidate’s long-term career goal is to become a university professor, where she can combine research in cellular quality control with educating the next generation of scientists and increasing diversity in the academy. She has designed her postdoctoral training to complement her graduate transcriptomics experience with experience in proteomics, biochemistry, and cell biology to address her research questions while becoming a well-rounded biologist. Training Environment: Rice University has an excellent training environment that supports interdisciplinary and inter-institutional research with other Texas Medical Center institutions, including full access to shared state-of-the-art equipment, while maintaining an intimate research setting inclusive of pedagogy, professional communication, and job market preparedness trainings. Dr. Bonnie Bartel, the project mentor, fosters a supportive environment that promotes scientific and professional development. She has an extensive publication and training record at the forefront of discoveries in phytohormones, microRNAs, and peroxisomes. Research: The goal of this project is to leverage the recent finding that functional peroxisomes are targeted for destruction by overzealous autophagy machinery when the peroxisomal chaperone and protease protein, LON2, is dysfunctional. This finding suggests the hypothesis that peroxisomal signals that promote pexophagy are degraded or refolded by LON2. The proposed experiments are designed to uncover mechanisms controlling peroxisomal turnover, to determine how this turnover facilitates overall cellular health, and to identify how peroxisome dysfunction signals to other organelles. Several interconnected approaches will be employed to achieve these goals. First, LON2 substrates will be identified and characterized, including chaperone, protease, and pexophagy-promoting substrates. Second, the proteomic landscape of cells housing dysfunctional peroxisomes will be surveyed to identify differentially accumulated proteins and associated alterations in other essential organelles. Third, transcriptomes will be analyzed to identify retrograde signaling from the peroxisomes to the nucleus, including the transcriptional responses that are induced when peroxisomes are compromised. These studies will incorporate predictive modeling and provide insight into the signaling components regulating pexophagy and cellular signaling responses that ensue when pexophagy is heightened or prevented. As many aspects of peroxisomal function are widely conserved, these experiments exploiting the advantages of the Arabidopsis model will likely provide insights useful for understanding the etiology of human peroxisome biogenesis disorders.

项目摘要 - 过氧化物体对细胞质量控制的影响 职业目标：候选人的长期职业目标是成为一名大学教授，她可以在这里 将细胞质量控制方面的研究与教育下一代科学家和增加 学院的多样性。她设计了博士后培训以补充她的毕业生 具有蛋白质组学，生物化学和细胞生物学经验的转录组学经验来解决她 研究问题同时成为一名全面的生物学家。 培训环境：赖斯大学拥有出色的培训环境，支持跨学科 以及与德克萨斯州其他医疗中心机构的机构间研究，包括完全访问共享 最先进的设备，同时维持包括教学法的亲密研究环境， 专业沟通和就业市场准备培训。邦妮·巴特尔（Bonnie Bartel）博士，该项目的精神， 促进了促进科学和专业发展的支持环境。她有一个 在植物激素，microRNA和 过氧化物体。 研究：该项目的目的是利用最近的发现，即功能性过氧化物是针对的 在过氧链烷和蛋白酶时，为了破坏过度狂热的自噬机械 蛋白质LON2功能失调。这一发现表明了一个假设，即促进的过氧物理体信号 pexophagy被LON2降解或重新折叠。提出的实验旨在发现 控制过氧化物球体周转率的机制，以确定这种周转率如何总体细胞 健康，并确定过氧化物体功能障碍信号如何与其他细胞器。几个相互连接 将雇用方法来实现这些目标。首先，将确定LON2基材，并 特征是，包括伴侣，蛋白酶和pexophagagy促进的底物。其次，蛋白质组学 将调查外壳功能失调的过氧化物体的景观，以鉴定不同的积累 其他必要细胞器中的蛋白质和相关改变。第三，将转录组分析为 识别从过氧化物组到细胞核的逆行信号，包括转录反应 当过氧化物体受到损害时会诱导的。这些研究将结合预测建模 并洞悉调节果胶和细胞信号反应的信号成分 当果蝇增强或预防时，可以保证。由于过氧化物体功能的许多方面是 这些利用拟南芥模型优势的实验广泛保守，可能会提供 洞察力有助于理解人过氧化物组生物发生障碍的病因。