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: 10429191
• 负责人: DurreShahwar Muhammad
• 金额: $ 10万
• 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/10429191
• 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; 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; Seeds; Signal Pathway; Signal Transduction; Surveys; System; Systems Biology; Texas; Training; Transcript; Universities; Yeasts; antioxidant enzyme; base; 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; 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：应聘者的长期职业目标是成为一名大学教授，在她能做到的地方 将细胞质量控制的研究与培养下一代科学家和提高 学院的多样性。她设计了博士后培训，以补充她的研究生 具有蛋白质组学、生物化学和细胞生物学方面经验的转录组工作经验 在成为一名全面发展的生物学家的同时研究问题。 培养环境：莱斯大学拥有良好的培养环境，支持跨学科 以及与其他德克萨斯医疗中心机构的跨机构研究，包括完全访问共享 最先进的设备，同时保持包括教育学在内的亲密研究环境， 专业沟通和就业市场准备培训。邦妮·巴特尔博士，项目导师， 营造有利的环境，促进科学和专业发展。她有一个 在发现植物激素、microRNAs和 过氧酶体。 研究：该项目的目标是利用最近的发现，即功能性过氧化物酶体是靶标 当过氧化体伴侣和蛋白酶被过度狂热的自噬机制破坏时 蛋白质LON2功能失调。这一发现提出了一种假设，即过氧化体信号促进 食欲性被LON降解或重新折叠。拟议中的实验旨在揭示 控制过氧化体周转的机制，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，将识别LON基板，并 具有特征性的，包括伴侣、蛋白酶和促进食欲的底物。第二，蛋白质组学 将对含有功能失调的过氧化物体的细胞景观进行调查，以确定差异积累 其他重要细胞器中的蛋白质和相关变化。第三，将对抄本进行分析以 识别从过氧化体到细胞核的逆行信号，包括转录反应 当过氧酶体受到损害时就会被诱导。这些研究将纳入预测性建模 并提供了对调节吞噬作用和细胞信号反应的信号组件的洞察 当食欲得到加强或预防时，就会发生这种情况。因为过氧化体功能的许多方面都是 这些广泛保守的实验利用了拟南芥模型的优势，可能会提供 有助于理解人类过氧化物酶体生物发生障碍的病因学的见解。