Identifying autophagy regulators in human cellular platforms using human pluripotent stem cell models

Autophagy is a vital homeostatic process essential for cellular survival and human health. It is implicated in myriad physiological and pathological conditions like development, immunity, longevity, cancer and neurodegeneration. Malfunction of this process is detrimental to the cells whereas stimulating autophagy promotes longevity and is beneficial in various transgenic disease models. Since therapeutic exploitation of autophagy has tremendous biomedical relevance, it is pertinent to understand the precise regulation of this process in the human system because emerging data indicate cell-type specificity of autophagy regulation. To undertake human-relevant biology, we are harnessing the power of human pluripotent stem cell models to establish isogenic human cellular platforms expressing an autophagy reporter. This system will be used to identify the molecular regulators of autophagy through high-content image-based screens using chemogenomics drug set and pharmacological probes with known cellular targets. Overall, we aim to study the landscape of autophagy in the human system at a physiological level and to gain mechanistic insights into human cell-specific regulation of autophagy. This will contribute to the fundamental understanding of this process that will have the potential for biomedical exploitation in future.