Peter Fuchs will put his grant to use by investigating a protein called epiplakin, which is found exclusively in epithelial cells where it binds to keratins. Keratins in turn are an essential part of these cells’ interior skeleton. Previous results suggested an important role of epiplakin in supporting the reorganization of keratins in injured liver and pancreas − in the absence of epiplakin, keratin forms aggregates in these organs. “We now plan to decipher the molecular details of epiplakin’s keratin-guiding functions in healthy and diseased epithelia. These findings could finally prove that missing epiplakin is the reason for the different outcomes of pathologies of the gastrointestinal tract”, says Peter Fuchs.

Sascha Martens will use his grant to investigate details of the cellular garbage disposal machinery autophagy, more specifically the autophagy of ubiquitinated proteins. Ubiquitin marks proteins for degradation in one of the cell’s waste recycling machinery, the proteasome. If the proteasome is inactive, the proteins are disposed of by the autophagy machinery to prevent the accumulation of cellular waste. For this, the proteins form aggregates that are surrounded by a membrane, much like garbage that is placed in a garbage bag. Sascha Martens and his group are now planning to answer the question as to how this aggregation and membrane-enclosure work in detail. “This is an exciting project and we are grateful to the FWF for funding it for the next four years”, says Sascha Martens.

Accidental activation of the immune system can result in hyper-inflammation and auto-immunity. To avoid this, certain molecules - called baseline-inhibitors - set an activation threshold. Supported by his FWF grant, Gijs Versteeg will explore this curtailing of the immune response. “In recent years, it has become very clear that immune cells are chronically over-activated in many diseases. This grant gives us the fantastic opportunity to understand how immune cells are regulated under physiological conditions so that we can better understand what goes wrong in disease. We hope to identify cellular factors for future therapeutic intervention”, says Gijs Versteeg.