Kulathu Lab

 

T-lymphocyte activation and adaptive immune respsonses - Regulation by ubiquitin and UBLs:

 

Acquired immunity against pathogens depends on the appropriate activation of T lymphocytes that form part of the adaptive immune system. Recognition of antigen in the right context activates lymphocytes and initiates an immune response to protect against pathogens and malignant cells. Whereas too little activation can result in recurrent infections, uncontrolled and sustained immune responses are the cause of chronic inflammatory diseases. Hence, lymphocyte development, activation and immune responses are all tightly regulated processes that are orchestrated by complex biochemical pathways. Research over the past 30 years to define these pathways in lymphocytes has focussed extensively on protein phosphorylation cascades. As a consequence, we know very little about the roles of other posttranslational modifications (PTMs) such as ubiquitin (Ub) and Ub-like modifiers (UBLs) within these pathways. Indeed, the few mouse models with genetic deletions of components of the Ub system show severe immunological disorders and defects in lymphocyte development underscoring important roles for ubiquitylation in lymphocytes.

In this research, funded by an ERC Starting Grant, we are addressing how ubiquitin and ubiquitin-like-modifiers (UBLs) regulate T cell function. This research will deliver fundamentally novel mechanistic insights into these PTMs while rewriting current concepts of signalling in lymphocytes. Ultimately, this work will inform therapies seeking to target lymphocyte activity in disease and strategies for immunotherapy.

 

 

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