AutophagosomeSealing · Ymr1 role in the Atg proteins release from complete autophagosomes

Autophagy is one of the major intracellular degradation processes and it is essential for cell survival in multiple stress conditions. As a result, this pathway plays a key role in the pathophysiology of numerous illnesses including neurodegenerative, cardiovascular, chronic inflammatory, muscular and autoimmune diseases, and some malignancies. Structures targeted to destruction such as protein aggregates, organelles and invading pathogens are sequestered into double-membrane vesicles called autophagosomes. Autophagosomes are formed through the concerted action of the autophagy-related (Atg) proteins at a site specialized location known as the phagophore assembly site (PAS). Despite this knowledge, the mechanism and regulation of autophagy remain largely unknown. The host laboratory has found that Ymr1, a phosphatase dephosphorylating phosphatidylinositol-3-phosphate, plays a key role in the regulation of autophagy. The main objective of this project is to elucidate the mechanism through which Ymr1 regulates autophagy. To achieve this goal, the applicant will exploit the experimental advantages of the yeast model and use in combination cutting-edge techniques in molecular biology, biochemistry, fluorescence microscopy and electron microscopy. The results will advance our knowledge on autophagy and in a long-term perspective they will provide the conceptual bases for the development of therapies or compounds aimed to regulate autophagy to the benefit of human health. Through the realization of the project, the applicant will strongly reinforce his professional maturity, diversity and independence, essential for starting his own research activity.