Atg1 as the master regulator of autophagy
The goal of this project is to understand how the central kinase regulating autophagy modulates the formation and termination of autophagosome biogenesis. Recent evidences point to a regulation through phosphorylation/dephosphorylation of components of the ATG machinery. Understanding which of these modifications is key for autophagy activation and inhibition, could provide more specific targets for autophagy modulation as well as biomarkers to follow autophagy progression in vivo. The PhD student will take advantage of the yeast system available at the host laboratory and will determine by mass spectrometry which proteins are phosphorylated by Atg1. Subsequently, phospho-mimicking and non-phosphorylable mutants will be generated before measuring autophagy using standard methods and determine which step of this pathway is affected. The PhD student will also test key findings in mammalian cells because Atg1 modifications could serve as biomarkers or eventually represent therapeutic targets.
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