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Peroxisomal impacts on cellular quality control Supplement

过氧化物酶体对细胞质量控制的影响补充剂

基本信息

批准号：
10820816
负责人：
DurreShahwar Muhammad
金额：
$ 1.89万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
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/10820816
关键词：
Academy Address Affect Arabidopsis Autophagocytosis Biochemistry Biogenesis Cell Nucleus Cells Cellular biology Communication Complement Defect Development Disease Environment Equipment Etiology Eukaryota Experimental Designs Fostering Functional disorder Genetic Transcription Goals Health Housing Human Institution Mammals Medical center Mentors Metabolic MicroRNAs Modeling Molecular Chaperones Organelles Pathway interactions Patients Peptide Hydrolases Physiological Plant Growth Regulators Plants Proteins Proteomics Publications Quality Control Reaction Reactive Oxygen Species Readiness Research Rice Scientist Signal Transduction Surveys Texas Training Universities career design experience experimental study insight inter-institutional job market next generation pedagogy peroxisome post-doctoral training predictive modeling prevent professor response supportive environment transcriptome transcriptomics

项目摘要

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 – 过氧化物酶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，在那里她可以将细胞质量控制研究与教育下一代科学家结合起来，并增加学院的多样性。她设计了博士后培训来补充她的研究生转录组学经验以及蛋白质组学、生物化学和细胞生物学经验来解决她的问题研究问题，同时成为一名全面的生物学家。培养环境：莱斯大学拥有支持跨学科的优良培养环境以及与其他德克萨斯医学中心机构的机构间研究，包括完全访问共享的最先进的设备，同时保持包括教学法在内的亲密研究环境，专业沟通和就业市场准备培训。项目导师 Bonnie Bartel 博士，营造促进科学和专业发展的支持性环境。她有一个在植物激素、microRNA 和过氧化物酶体。研究：该项目的目标是利用功能性过氧化物酶体的最新发现当过氧化物酶体伴侣和蛋白酶被过分热心的自噬机制破坏时蛋白质 LON2 功能失调。这一发现提出了这样的假设：过氧化物酶体信号促进 pexophagy 被 LON2 降解或重折叠。拟议的实验旨在揭示控制过氧化物酶体周转的机制，以确定这种周转如何促进整体细胞健康，并确定过氧化物酶体功能障碍如何向其他细胞器发出信号。几个相互关联的将采用各种方法来实现这些目标。首先，将鉴定 LON2 底物并特征，包括分子伴侣、蛋白酶和促进自噬的底物。二、蛋白质组学将调查容纳功能失调的过氧化物酶体的细胞景观，以确定差异积累蛋白质和其他重要细胞器的相关变化。第三，将分析转录组识别从过氧化物酶体到细胞核的逆行信号传导，包括转录反应当过氧化物酶体受到损害时会诱导。这些研究将纳入预测模型并深入了解调节自噬和细胞信号反应的信号成分当食肉癖被加强或被阻止时，就会发生这种情况。由于过氧化物酶体功能的许多方面广泛保守，这些利用拟南芥模型优势的实验可能会提供对于理解人类过氧化物酶体生物发生障碍的病因学有用的见解。