CAREER: Understanding Peroxisomal Stress Responses

This research will investigate how eukaryotic cells sense and respond to malfunctioned organelles, such as peroxisomes. Peroxisomes are essential subcellular organelles involved in lipid metabolism and hydrogen peroxide detoxification. Despite the crucial role of peroxisomes in maintaining cellular and metabolic homeostasis, our knowledge on how cells cope with peroxisome dysfunction is largely missing.

Using genetic and biochemical approaches, this project aims to uncover novel peroxisome surveillance pathways and a cascade of stress responses induced by defective peroxisomes. Through this project, the investigators will integrate peroxisome research into innovative educational activities allowing students to gain hands-on experiences in genetic and cell biology research.

These educational activities include: 1) Developing an innovative undergraduate laboratory course to provide students with hands-on experience in genome editing and imaging techniques through course-based undergraduate research experiences; and 2) Engaging undeclared students in genetic and cell biology research through partnership with “The Sky is the Limit” learning community. These integrated education programs will engage larger and more diverse groups of undergraduate students in biology research, and make basic research more inclusive.

Peroxisomes are important, yet least studied subcellular organelles in all eukaryotic cells. Dysregulated peroxisomal protein translocation can lead to impaired organelle function and disrupted cellular homeostasis. However, little is known about how cells surveil and respond to impaired peroxisomal protein import.

This project will utilize state-of-the-art genome-wide CRISPR screening and TurboID proximity labelling techniques to map novel peroxisome stress response pathways and identify mechanisms underlying cellular homeostatic response to defective peroxisomal protein import. Several novel hypothesis will be examined, including: 1) How peroxisomal membrane proteins relay stress signal from the peroxisome to the nucleus; and 2) How serine/arginine-rich splicing factors activate cellular adaptive responses upon peroxisomal stress.

Overall, the results of this research will likely have an important and positive impact on the protein translocation stress research field and may significantly advance our understanding of cellular adaptation to dysregulated peroxisomal protein import.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.