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We investigate the implications of proteasome-catalysed peptide splicing 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.

Furthermore, by applying a multi-scale and multi-disciplinary approach – thereby combining in silico, in vitro and in vivo strategies – we study how proteasome isoforms regulate the inflammation in the intracellular and extracellular space by degrading proteins and producing (pro)inflammatory peptides.

PhD students

Bei fang Teo (PhD)

People

Research Associate

Camila  Barbosa

Postdoctoral Research Associate

Michele  Mishto

Professor in Immunobiology

Themes

MHC-I antigen processing and presentation
MHC-I antigen processing and presentation

The proteasome is the core of the ubiquitin-proteasome system and responsible for 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 (APP). The proteasome is only the first step of the APP pathway. We investigate APP steps and how they impinge upon the recognition by CD8+ T cells.

    Proteasome-catalysed peptide splicing
    Proteasome-catalysed peptide splicing

    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 developed a novel method for spliced peptide identification and discovered its relevance in the antigen presentation.

      Extracellular proteasome
      Extracellular proteasome

      The proteasome is active also in the extracellular space where it can cleave osteopontin and release peptides that promote cell migration. We showed evidence that this mechanism could play a role in multiple sclerosis.

        Proteasome isoforms
        Proteasome isoforms

        There are several proteasome isoforms, which carry out preferential functions in different cell types. We investigate the biochemistry behind their function.

          Publications

            Funders

            1. CRUK Programm Foundation Award (2020-2026)
            2. BRC3-IIa (2019-2022)
            3. MPI-BPC collaborative contract (2018-2019)
            4. CRUK-KHP Development fund (2018-2019)
            5. Monash-KCL Seed fund (2018-2019)
            6. KCL-Charite joint call seed fund (2019-2020)

            People

            Research Associate

            Camila  Barbosa

            Postdoctoral Research Associate

            Michele  Mishto

            Professor in Immunobiology

            Themes

            MHC-I antigen processing and presentation
            MHC-I antigen processing and presentation

            The proteasome is the core of the ubiquitin-proteasome system and responsible for 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 (APP). The proteasome is only the first step of the APP pathway. We investigate APP steps and how they impinge upon the recognition by CD8+ T cells.

              Proteasome-catalysed peptide splicing
              Proteasome-catalysed peptide splicing

              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 developed a novel method for spliced peptide identification and discovered its relevance in the antigen presentation.

                Extracellular proteasome
                Extracellular proteasome

                The proteasome is active also in the extracellular space where it can cleave osteopontin and release peptides that promote cell migration. We showed evidence that this mechanism could play a role in multiple sclerosis.

                  Proteasome isoforms
                  Proteasome isoforms

                  There are several proteasome isoforms, which carry out preferential functions in different cell types. We investigate the biochemistry behind their function.

                    Publications

                      Funders

                      1. CRUK Programm Foundation Award (2020-2026)
                      2. BRC3-IIa (2019-2022)
                      3. MPI-BPC collaborative contract (2018-2019)
                      4. CRUK-KHP Development fund (2018-2019)
                      5. Monash-KCL Seed fund (2018-2019)
                      6. KCL-Charite joint call seed fund (2019-2020)

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                      Blood Cancer UK

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                      Max Planck Institute