Cells possess the ability to selectively clear out damaged or excess cellular components, through a process known as selective autophagy. This mechanism is critical for maintaining cellular homeostasis, and its defects have been linked to diverse human disorders, including neurodegeneration and metabolic disease. Despite important progress in the field, the upstream regulators that dynamically control the activation and termination of selective autophagy remain poorly understood.
In TiGeR (Time-Resolved Functional Genomics of Selective Autophagy Regulation), we aim to map, on a genome-wide scale, how yeast cells regulate different forms of selective autophagy: mitophagy, ribophagy and ER-phagy. By combining high-throughput microscopy with deep learning, we will perform time-resolved single-cell genome-wide profiling to determine not just whether the respective genes affect these processes, but when and how: at the start, during the response, or at its termination. As part of the project, I will spend time at the University of Toronto, in the laboratories of Prof. Charles Boone and Prof. Brenda Andrews, before returning to CanCell to integrate the data and validate key candidate regulators. By revealing the regulators that control selective autophagy dynamics, we aim to build a resource for the field to better understand how these processes are orchestrated in time.