Peroxisomal quality control mechanisms

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.