Michele Mishto, Dr. rer. Nat.
Senior Lecturer in Immunobiology
Proteasome is the core of the ubiquitin-proteasome system and responsible of the degradation of the majority of the protein in the cytosol. It is therefore involved in a large variety of metabolic pathways, including inflammation and antigen processing and presentation.
Proteasome produces fragments by canonical peptide-bond hydrolysis or by peptide splicing. Indeed, proteasome can break a protein and reshuffle its sequence by combining non-continuous fragments, thereby generating spliced peptides. By peptide splicing, proteasome significantly enlarges the antigenic landscape of a cell.
We investigate the implications of this mechanism in tumour immunology, autoimmunity and in the CD8+ T cell response during infection, with the long-term aim to improve the efficacy of immunotherapy and vaccine development.
By applying a multi-scale and multi-disciplinary approach – thereby combining in silico, in vitro and in vivo strategies – we also study the ability of proteasome isoforms to regulate the inflammation in the extracellular space by producing peptides with an enhanced ability to promote leucocyte chemotaxis, adhesion, etc.