PROPPIN regulation in cancer and autophagy
Objectives: The goal of this project is to acquire new knowledge about the signalling networks regulating autophagy in health and cancer. Human PROPPINs, referred to as WIPI (WIPI1-4), are associated with age-related human diseases, such as cancer and neurodegeneration, and function as essential phosphatidyl-3-phosphate (PI3P) effectors in autophagosome biogenesis. However, it remains unknown how all 4 WIPIs are regulated to precisely fullfil their function in autophagy. The defined goals of this project are 1) to identify the signalling cascades governing the differential functions of the 4 WIPIs in autophagy, and 2) to unveil the mechanism of signal-regulated recruitment of human WIPIs to the forming autophagosome. As WIPIs are aberrantly expressed in cancer and mutations in both, WIPI3 and WIPI4 have been associated with neurodegeneration, detailing the molecular regulation and function of WIPIs in the process of autophagy will provide critical insights on how the process of autophagy could be precisely targeted during therapeutic interventions.
To identify signalling cascades regulating human WIPIs, the PhD student will employ molecular and cell biology techniques, including functional high-throughput imaging and screening procedures, live-cell, confocal and electron microscopy, using different mammalian cells (e.g. tumor cell lines, primary cells), and the model organism Caenorhabditis elegans.