Mechanisms and hierarchy in autophagosome formation

In my lab we want to understand how the cellular waste disposal system, called autophagy, works. Defects in autophagy have been associated with several human diseases, including neurodegenerative disorders and cancer. During autophagy, membranes are initiated at the pre-autophagosomal structure close to the vacuole. The formation of these organelles called autophagosomes is regulated by the Atg1 kinase complex present at and part of this structure, which itself is under the control of the target of rapamycin kinase. Several components essential for autophagy induction have been identified in yeast and mammals, yet the mechanisms underlying this event remain elusive. As autophagosomes are not constitutively present in a cell but only formed upon certain stimuli, studying the formation of these organelles also helps us to understand organelle biogenesis in general. Mechanistic insight into the regulation of autophagosome formation is key to understand how autophagy is regulated. Our goal is to understand the signaling events inducing and regulating autophagic cargo uptake into autophagosomes and their subsequent delivery to the vacuole. We use a combination of biochemical, genetic and cell biological approaches including novel fluorescent microscopy methods. We will create an artificial autophagy cargo, which will allow us to study the players needed for packaging as well as the order of events from the early beginning of the process, which wasn`t possible to study to date. Using such a novel system provides a niche for our research. These approaches will greatly advance our understanding of autophagy regulation and address a number of key questions on the regulation of organelle formation in general.