Innovating Works

MMAF

Financiado
Molecular mechanisms of autophagosome formation
During autophagy initially small double membrane-bound structures expand and adopt cup-like shapes. These cup-shaped structures fuse at their rims to give rise to autophagosomes within which cytoplasmic material is enclosed. Subse... During autophagy initially small double membrane-bound structures expand and adopt cup-like shapes. These cup-shaped structures fuse at their rims to give rise to autophagosomes within which cytoplasmic material is enclosed. Subsequently autophagosomes fuse with endosomes and lysosomes and the content and the inner membrane are degraded. Autophagy serves to recycle essential building blocks during starvation, to degrade damaged organelles, to clear cells of protein aggregates and to kill intracellular microorganisms. Little is known about the mechanisms by which cells bend and remodel membranes into autophagosomes. The action of a complex containing type III PI3K activity is essential for the initiation of autophagosome formation. During expansion of the initial double membrane bound structure the Atg8 and Atg12 conjugation systems play important roles. A further protein that is essential for autophagosome formation is the transmembrane protein Atg9. We will investigate the impact of individual PI3K complex subunits, the Atg8 and Atg12 conjugation systems and Atg9 on membrane morphology in vitro. We will analyse membrane shape changes and micro-domain formation using artificial small and giant liposomes by electron and light microscopy. We will introduce targeted mutations that are designed to interfere with membrane shape changes or micro-domain formation. Furthermore, where necessary, we will solve the structure of individual subunits or complexes by x-ray crystallography. We will further verify our in vitro findings in cell culture systems. Our results will give important insights into autophagy and organelle formation in general. ver más
29/02/2016
UNIVIE
1M€

Línea de financiación: concedida

El organismo FP7 notifico la concesión del proyecto el día 2016-02-29
Presupuesto El presupuesto total del proyecto asciende a 1M€
Líder del proyecto
UNIVERSITAT WIEN No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5