Personal Statement
The focus of my research and teaching is on infectious diseasesa. I lead a diverse group of researchers using molecular techniques to study virus infection and interventions in man and animals. This includes COVID-19, Influenza and respiratory syncytial virus (RSV). Using the high containment facilities at Liverpool I have established precliical models of virus diseases including Influenza and COVID-19 and am using them to develop theapeutics and vaccines.

I trained as a molecular biologist, applying molecular techniques to study virus/host interactions, specifically the immune response. A large part of my career has been spent studying pathogenesis and virus-host interactions, with a particular focus on the herpesvirus family.
With Tony Nash, I developed murine gammaherpesvirus in mice as a means of studying authentic host-virus interactions, exploiting the power of virus reverse genetics and KO mouse technology.
More recently my research has moved to focus on virus-host interactions in the respiratory tract, using other respiratory pathogens such as influenza A virus, RSV and coronaviruses (SARS-CoV-2). I have developed an integrative toolkit and pathway with which to do this. I use conventional and molecular techniques to analyse the course of virus infection combined with big data techniques and informatics to relate the function of viral determinants with host defence responses. The ultimate aim is to translate this into novel interventions and vaccines.

I teach Veterinary, Medical and Life Science students up to Masters level. I have previously served as external examiner for Edinburgh University (Bsc (Hon) Infectious Disease) and Imperial College London (MSc Virology). I have been examiner for 50 PhD theses both in the UK and internationally.
My Laboratory currently consists of 1 PDRA and 4 PhD students. I have previously supervised 38 PhD students and 4 MD students from the UK and Internationally to completion many of whom are now academics, group leaders, or working in Industry.
At Liverpool I am Chair the University Biohazards Committee. I have previously been Head of Department, Head of School and Chair of the University Animal Welfare and Ethical Review Body. I am Academic Editor for PLoS ONE, on the Scientific Advisory Board of the Roslin Institute and have served on UK research council funding and review panels since 2004. I have also appeared on UK National TV giving expert opinion on Influenza vaccination.

Research Overview
1. Pathogenesis and prevention of SARS-CoV-2 infection
With the emergence of SARS-CoV-2 and the COVID-19 pandemic I have developed the K18-hACE2, hamster and rat models of SARS-CoV-2 infection and am using them to study pathogenesis, vaccines and therapeutic interventions. I have MRC, Wellcome Trust, Innovate UK, and industry-funded projects studying the pathogenesis of new SARS-CoV-2 variants, developing novel SARS-CoV-2 drugs and developing nanobody therapies. I am working in collaboration with Prof Andrew Owen (UoL) in development of therapeutics and with a number of external partners including, Jim Naismith (Rosalind Franklin institute, Oxford), Leo James (LMB Cambridge), Ultan Power, (Queen’s Belfast), Miles Carrol (Oxford) and several SMEs. This has led already to significant outputs e.g Brevini et al. (2023) Nature. 615. 124-142, Gaynor et al. (2023) Nature Comms. and Huo et al (2021). Nature Comms. 12, 5469 and identification of candidate therapeutics to take forward to human clinical trials. The nanobody work was also awarded a Royal Society of Chemistry Horizon Prize 2022

2. The role of autophagy in virus pathogenesis
With Tom Wileman (Quadram Institute Bioscience) and funded by a BBSRC project grant, 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. We have shown that LAP-deficient mice are more susceptible to flu infection and are mapping the changes in the innate and adaptive response. Wang et al (2021) EMBO Journal. e105543

2. Innate host-defence function in the respiratory tract
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 (one MRC DTP iCASE with Sisaf Ltd), 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. Akram, et al. (2018). Mucosal Immunology, 11. 71-81.

4. The use of Bacteroides outer membrane vesicles (OMVs) in respiratory vaccination.
With Simon Carding (Quadram Institute Bioscience) I have shown that Bacteroides spp OMVs expressing recombinant proteins are extremely effective in generating a strong specific mucosal IgA and IgG response We are now taking this forward to develop potential vaccine candidates against respiratory pathogens starting with influenza A virus and peste de petit ruminants. Carvalho, et al. (2019). Journal of Extracellular Vesicles. 8:1,

5. Malignant Catarrhal Fever in Cattle
Malignant catarrhal fever is a fatal lymphoproliferative disease of cattle, bison and deer. I cloned and developed the first sequence of ovine herpesvirus 2 which is the causative agent. I have subsequently developed a toolkit to study OvHV-2 and determined that OvHV-2 is endemic in non-diseased cattle, being vertically as well as horizontally transmitted. This defines a new paradigm and transforms the understanding of this disease. The ultimate goal is to design a vaccine and therapies for malignant catarrhal fever. I have two externally funded studentships working on MCF and developing a subunit vaccine based on recombinant poxviruses for use in farmed Bison where MCF is a particular problem. As part of this I am working with local veterinarians and Bison producers.