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Our research integrates diverse techniques and approaches from cell culture, virology, molecular biology, biochemistry and bioinformatics to uncover novel innate inhibitors and dependency factors of HIV, Influenza, SARS-CoV-2, and other viruses. We also seek to understand these host factors’ mechanism of action at the cellular and molecular levels. Identifying host-viral interactions and molecular mechanisms involved permits to clarify principles that explain viral infection, replication and spread.

The balance between dependency and restriction host factors dictate cell permissivity and thus transgene expression. This knowledge will then be applied to the optimisation of vectors for gene therapy and regenerative medicine.

Themes

HeLa cells with dapi-stained nuclei (blue) and expressing HIV-1 Gag (green) and APOBEC3G (Red)
Uncovering novel host factors that regulate HIV-1

We are studying natural human variation to further understand and discover new host regulators of HIV-1 infection and replication. Subtle differences in the human population have been captured in an extensively characterised library of induced Pluripotent Stem Cells (www.hipsci.org). These cell lines display different infection phenotypes. Correlating genotypes that explain the observed extreme phenotypes in a systems approach will permit to identify HIV-1 host regulatory factor candidates. These we will then be validated and further studied in vitro models.

    Viruses computer illustration
    Development of lentiviral vectors to target specific cells in vivo

    We will use the breadth of knowledge generated in HIV research and particularly within our department to develop lentiviral vectors that target specific cells in vivo. This may revolutionise the paradigm of gene and cell therapy: current medicines are highly costly which involve patient target cell isolation, correction of genetic mutations or addition of a new/repaired gene, and reintroduction of the altered cells into the patient. In vivo gene therapy would be a cheaper process, with a single-dose medicine that could be used for many patients. We are currently developing vectors that can specifically target T cells. This will allow the genetic modification of T cells to express chimeric antigen receptors (CAR-T Cells) and ultimately their use in cancer treatment.

      Publications

      Themes

      HeLa cells with dapi-stained nuclei (blue) and expressing HIV-1 Gag (green) and APOBEC3G (Red)
      Uncovering novel host factors that regulate HIV-1

      We are studying natural human variation to further understand and discover new host regulators of HIV-1 infection and replication. Subtle differences in the human population have been captured in an extensively characterised library of induced Pluripotent Stem Cells (www.hipsci.org). These cell lines display different infection phenotypes. Correlating genotypes that explain the observed extreme phenotypes in a systems approach will permit to identify HIV-1 host regulatory factor candidates. These we will then be validated and further studied in vitro models.

        Viruses computer illustration
        Development of lentiviral vectors to target specific cells in vivo

        We will use the breadth of knowledge generated in HIV research and particularly within our department to develop lentiviral vectors that target specific cells in vivo. This may revolutionise the paradigm of gene and cell therapy: current medicines are highly costly which involve patient target cell isolation, correction of genetic mutations or addition of a new/repaired gene, and reintroduction of the altered cells into the patient. In vivo gene therapy would be a cheaper process, with a single-dose medicine that could be used for many patients. We are currently developing vectors that can specifically target T cells. This will allow the genetic modification of T cells to express chimeric antigen receptors (CAR-T Cells) and ultimately their use in cancer treatment.

          Publications

          PhD Students

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