Innate host defence: a playing field for the ubiquitin machinery

The Gyrd-Hansen laboratory studies molecular mechanisms governing pro-inflammatory signalling during innate immune responses. Through this, they aim to understand the molecular mechanisms that on one hand protect against pathogens, but that also contribute to chronic inflammation, tumor development and cancer progression. A central focus of the lab is to elucidate the role and regulation of non-degradative ubiquitin modifications in these processes. Ultimately, they aim to identify ubiquitin-handling factors that can be targeted to modulate inflammation and antagonize cancer. Professor Gyrd-Hansen’s recent work has focused on the role of Met1-linked ubiquitin chains (also known as linear ubiquitin chains) in inflammatory signaling. These chains are generated by the Linear UBiquitin Assembly Complex (LUBAC), which is a key component of inflammatory signaling pathways, including those activated downstream of the cytoplasmic PRRs NOD1 and NOD2 that serve as sensors for intracellular bacteria. They have uncovered and characterised several factors that regulate the function of LUBAC in signaling. Future work in the group will focus on elucidating the function, regulation and interplay of individual ubiquitin chain types (of which there are at least eight) in the cellular response to infection.