The project centres on genetic diversity present in families of genes involved in immune responses and disease resistance, and the related functional implications of this variation. We already have a good understanding of the complexities of the cattle MHC genes, although assessment of MHC diversity in different breeds and populations is on-going. These genes are centrally involved in both adaptive and innate immune responses, interacting with T cell receptors and natural killer (NK) cell receptors. Detailed analysis of NK cell receptor genes is essential to gain an understanding of the complex interplay of NK cells, receptors, their ligands and pathogens. Characterisation of these genes and their ligands is the main component of the project. This will give an insight to the functional implications of genetic variation and will lead on to further population-based studies. In addition to this work the project encompasses some MHC typing essential for maintenance and development of the IAH genetically defined cattle herd.

To create fowlpox-based candidate DIVA vaccines against PPRV, establish the degree of immune response of these vaccines and the optimal set of proteins to express from the recombinant. To set up appropriate C-ELISAs that recognise infection and/or vaccination separately. To develop flow-capture-based penside tests for PPRV antigen. In Uganda: To conduct the field trial of the candidate DIVA vaccine against PPR. To characterize the strains of PPRV circulating, and their extent of spread, in Uganda (genetic analysis). To validate the next generation of ELISA tests to differentiate vaccinated from infected animals (DIVA tests). To validate penside diagnostic tests for PPR. To introduce real-time PCR for the diagnosis of PPR and sheep/goat pox into the lab in Uganda.

Swine influenza attracts considerable attention because of the threat of zoonotic infections causing human pandemics. During the pandemic, a fear that viruses emerging from pigs may infect people resulted in the widespread destruction of animals in some countries and trade bans. Consequently, the insidious effects of this highly prevalent virus on the health and welfare of pig populations, estimated to increase the cost of production by £7 per finished pig, have not been given due regard. The primary disease caused by influenza virus in usually mild, but results in greater susceptibility to secondary infections. Vaccination will be a key control measure for influenza in pigs to improve general herd health. Through our studies we will develop a more detailed understanding of the dynamics of virus transmission and the consequences of transmission and vaccination in driving viral evolution. During these studies we will also define a range of parameters, for example local and systemic immune responses and sites of virus replication, which are associated with the onset and cessation of transmission.

This proposal aims to examine the role of Marek's disease virus-encoded micro RNAs in the pathogenicity of Marek's disease, a highly contagious neoplastic disease of poultry characterised by the development of rapid-onset lymphomas. As part of this project, we have identified several novel microRNAs encoded by the members of the genus Mardivirus including 13 in MDV-1, 17 in MDV-2 and 11 in herpesvirus of turkeys (HVT), a vaccine strain closely related to MDV-1 and MDV-2. All these microRNAs are expressed at very high levels in infected/transformed cells, suggesting a direct role for these microRNAs in the biology of the virus infection and disease. In this proposal, we aim to carry out detailed examination of the targets for these microRNAs, analyse their expression in MDV-transformed cell lines/tumours and use the reverse genetics system of bacterial artificial chromosome (BAC) clones of the 3 serotypes to examine the role in the natural target host disease models.

Eimeria belong to the phylum Apicomplexa, which include many devastating parasites of man and livestock. Coccidiosis caused by the Eimeria species is the single most economically important protozoan disease of poultry throughout the world and new methods of control are required. The development of novel control strategies will be facilitated through a combination of fundamental and applied biology, supported through the development of appropriate tools. Recent progress in genomic and proteomic projects led by IAH scientists, supplemented by the development of reverse genetic techniques to manipulate the parasite genome, now provide a solid platform for these studies. Three key strands of study underpin this work package to define Eimeria components central to host interaction with relevance to future control strategies. Firstly, the endemic distribution of the Eimeria species and the longevity of the environmental phase of the lifecycle demand stringent biological control during reproduction for laboratory resources. The production of parasites and parasite derived materials will continue to support genomic, transcriptomic, proteomic and functional projects within IAH and in collaboration with other scientists. Output from these studies will be utilised in the identification and characterisation of key parasite molecules including surface antigens and proteins integral to parasite motility, adhesion, invasion and replication. Secondly, antigens identified will be rationally prioritised for inclusion in novel control strategies, informed by ongoing competitively funded molecular characterisation and genetic mapping projects. Finally, we will capitalise on the development of reverse genetic tools for Eimeria to inform ongoing studies and investigate applications as vaccine delivery vehicles in programmes protective against Eimeria and other pathogens of poultry.