Simon Brackenridge

After obtaining a BSc in Molecular Biology from the University of Edinburgh, I moved to Oxford to take up a DPhil at the Sir William Dunn School of Pathology, studing transciption termination and 3' end formation in eukaryotic cells in the laboratory of Nicholas Proudfoot. Having stayed on in the Proudfoot lab to finish up a number of projects, I then worked in the laboratory of Gavin Screaton at the Weatherall Institute of Molecular Medicine, investigating non-canonical splicing in the human Fibroblast Growth Factor Receptor genes. When Gavin dpearted for pastures new (Imperial College), I stayed at the WIMM, joining the laboratory of Professor Sir Andrew McMichael, as part of the NIH-funded Center for HIV/AIDS Vaccine Immunology (CHAVI). My initial role was part of a collaboration with Ed Southern's Oxford Gene Technology, who were developing novel microarray technology for the analysis of gene expression in blood samples from people living with HIV. As the CHAVI collaboration developed into the Center for HIV/AIDS Vaccine Immunology, Immunogen Discovery (CHAVI-ID), I became involved more with immunology research than molecular biology.  My first immunology project was focused on investigating a possible role for the Human Leukocyte Antigen C (HLA-C) in controlling the replication of HIV and delaying progression to AIDS. This was followed by work attempting to identify ligands for the human killer cell immunoglobulin like receptor, three Ig domains and short cytoplasmic tail 1 (KIR3DS1) protein. More recently, I have been involved in studying presentation of pathogen peptides by the Human Leukocyte Antigen E (HLA-E) protein, including work to understand how Cytomegalovirus (CMV) manipulates HLA-E expression to evade detection by the host immune system.

Unlike the highly polymorphic classical HLA-A, B and C alleles, which present peptides to CD8+ T cells, HLA-E has limited polymorphism. This would allow HLA-E-based immunotherapeutics to be to be widely applied, unlike therapeutics based on HLA-A, B or C, which need to be tailored to match the patients HLA type. The initial focus of the McMichael lab was to develop theraputics against viral infections, starting with HIV. Working as part of the NIH-funded Delaney Collaboratory of Researchers for Eradication (CARE), I have been particularly involved in characterising the specificity of antibodies raised against HLA-E presenting particular HIV peptides that have been isolated by our collaborators in the laboratory of Barton Haynes (Duke University, North Carolina). On joining the Centre for Immuno-Oncology, the McMichael laboratory has broadened its focus to include the development of HLA-E-based therapeutics for cancer.