Analysis of Atg1/ULK1 function in autophagy

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 function and regulation of the key kinase in autophagy, Atg1/ULK1 and the formation of autophagosomes is essential to understand how autophagy is regulated. Our goal is to understand the mechanism of Atg1/ULK1 function. We use a combination of biochemical, genetic and cell biological approaches including quantitative mass spectrometry techniques as well as fluorescent microscopy methods. We furthermore established synthetic in vivo approaches as well as in vitro reconstitutions to dissect the mechanism of Atg1/ULK1 function from yeast to mammals. Insights gained from these approaches will then be verified in yeast and mammalian cell culture systems in vivo. 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.

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