Membrane identity changes in control of contact site formation

The formation of membrane contact sites between organelles is a crucial aspect of cell biology, mediating interorganellar lipid transport. Importantly, the identity of organelles is determined in part by phosphoinositides, a small family of interconvertible phospholipids that act as signposts of membrane identity. I hypothesise that the formation of contact sites is regulated by unique changes to the membrane identity of organelles. To address this concept, peroxisome-lipid droplet membrane contact sites offer a unique opportunity to gain mechanistic insights into phosphoinositide conversion pathways that control their formation. This specific contact is of key physiological relevance for its role in the transfer of very-long-chain-fatty-acids from lipid droplets to peroxisomes, typically in response to oxidative stress and high energy demand.

Through a unique combination of cell biological perturbation, discovery approaches, and in vitro reconstitution, I will gain a mechanistic and regulatory understanding of phosphoinositide identity changes during membrane contact site formation. The outcome of my approach will be a framework towards understanding the regulation of contact site formation between membranes with distinct identities. Moreover, it will form the basis for a better understanding of fundamental aspects in cell biology with profound implications for health and disease.