Atypical ubiquitin chains in immunometabolism

Despite it is now known that immune cells reprogram their cellular metabolism for exerting specific immunological functions, we still lack a deep understanding of the molecular mechanisms implicated in immunometabolism.

Protein ubiquitination, an essential posttranslational modification, regulates virtually all immune cells, but its specific roles in the metabolism of immune cells remain poorly characterized.

We have now identified a novel ubiquitin-related enzyme, a deubiquitinase, which according to our preliminary data, appears to have important roles in immunometabolism.

We hypothesize that this can significantly impact macrophage functions and in turn, atherosclerosis, an inflammatory disease, and a leading cause of death worldwide.

Our data also suggest that these molecular events are dependent on atypical ubiquitination, a protein ubiquitination event where the chains of ubiquitin are linked unusually. Notably, the role of atypical ubiquitin chains in biology is virtually unknown. Thus, our project addresses significant knowledge gaps across the immunometabolism and ubiquitin research fields.

We have designed a comprehensive study supported by our extensive expertise in animal experimentation, immunity, and ubiquitin-related research.

We will use cutting-edge technologies, animal models, and ex vivo mouse and human studies to conclusively reveal an unforeseen role for atypical ubiquitination in immunometabolism and to test its pathophysiological role in vivo.