We are a research laboratory located in the Blizard Institute at Queen Mary University of London with a focus on the structural and biophysical characterisation of the ubiquitin system.
Ubiquitin is a small protein which is used for posttranslational modifications, a process known as ubiquitylation. The attachment of ubiquitin chains to target proteins plays fundamental roles in almost all aspects of cellular life. The Stieglitz lab aims to understand in molecular detail how ubiquitin modifications work in the context of infection and cell autonomous immunity. Our group explores the mechanisms, the regulation and the specificity of the ubiquitin system in inflammatory pathways. A second area of research is the structural and functional investigation of bacterial ubiquitin ligases. Several pathogens exploit the host ubiquitin system to specifically undermine and subvert defence mechanisms of the infected cell. We are interested to elucidate the structural biology of ubiquitylation which takes place at the interface of bacterial pathogenesis and innate immune responses. The Stieglitz lab is using cryo-EM, X-ray crystallography and NMR in combination with biophysical techniques such as ITC or fluorescence spectroscopy to reveal the kinetic and structural mechanisms of the ubiquitylation machinery. Our research programme aims to provide knowledge relevant for the development of new therapeutics in auto immune diseases and the intervention of antimicrobial resistance.
Subversion of the NFkB pathway by IpaH ligases from Shigella. Activation of the NFkB pathway involves different ubiquitin ligases (green) which catalyse ubiquitination (green circles) of several components after TNF receptor stimulation (left panel). Infection with Shigella results in ubiquitination (red circles) of host ligases and other components of the NFkB pathway by bacterial ubiquitin ligases (red), thereby diminishing the immune response (right panel).