Prof James Stewart PhD

With Tom Wileman (Quadram Institute Bioscience) and funded by a BBSRC project grant (one PDRA), I am studying the influence of non-canonical autophagy (LC3-associated phagocytosis, LAP) on virus pathogenesis and the development of inflammation. This uses KO and conditional KO mice models combined with viruses expressing cre recombinase to dissect out the influence of different autophagy pathways and cell types. With a joint PhD studentship, we have generated preliminary data showing that LAP-deficient mice are more susceptible to flu infection and are mapping the changes in the innate and adaptive response

BPIFA1/SPLUNC1 is secreted into the mammalian respiratory tract. I have established model systems for studying SPLUNC1 function using knockout mice, conditional/inducible KO mice and 3D tracheal epithelial cultures (mTEC). I have shown that SPLUNC1 restricts influenza virus infection by reducing binding and entry of influenza virus into cells (Mucosal Immunology). I have also shown that, unexpectedly, SPLUNC1 plays a critical role in the generation of virus-specific immunity (antibody and CD8 T cells) and hence immunity to re-infection. RNAseq and high-resolution label-free quantitative proteomics followed by informatics has revealed pathways and molecular signatures associated with SPLUNC1 action. Funded by a BBSRC grant (one PDRA), and supported by two PhD students, I am now identifying SPLUNC1 binding partners and assessing the function of SPLUNC1 (and associated signatures) in immunity against re-infection. SPLUNC1 may therefore have therapeutic potential.

With Hussein Ahmed (Cairo, Egypt) and Mohammed Munir (Pirbright Institute) and funded by a Newton Fund Institutional Links grant (one PDRA) I am developing novel rapid multiplexed diagnostics and multi-valent vaccines for viruses that cause significant welfare and economic impact in Egypt – specifically avian influenza, Newcastle disease and IBV.