Prospectus – Vet Graduate School The Institute for Comparative Medicine This new Institute has been established as the research division of the School, and to promote an integrated approach to research strategy and planning. The Institute has a strong and diverse research profile much of which is directed towards the fundamental problems common to Veterinary and Medical diseases. Research within the Institute of Comparative Medicine is organised into four themes (Infection and Immunity, Wellcome Centre for Molecular Parasitology, Comparative Pathobiology, Animal Health). These four research themes encompass nine focussed sections that represent the major research activity of the Institute. Resources • Well equipped laboratories • Library • Study areas • PC & On-line access Research Groups Infection and Immunity (Contact: Prof. Andy Tait; [email protected]) Molecular and Immunobiology of Parasitism (Contact Prof. E. Devaney; [email protected]) The research of this group, which includes the Wellcome Centre for Molecular Parasitology (contact Prof. D.Barry; [email protected]), focuses on nematodes and protozoa, and involves molecular and immunological approaches to the understanding of their biology, immune evasion and pathogenesis. The fundamental knowledge which flows from these studies is being applied in the development of novel chemotherapeutics and vaccines. Research on nematodes uses C.elegans as a model system to investigate the development of the cuticle and to analyse the functional roles of key parasite-derived molecules. This research is directed at both the functional analysis of factors determining the expression of environmentally and developmentally regulated genes, as well as parasite regulation of the host immune response. The protozoan research spans the topics of parasite genetics, surface molecule variation, control of parasite proliferation and pathogenesis, and parasite control of host cell proliferation. These themes share a focus on processes fundamental to the growth and survival of parasites and their interaction with the host. Virology (Contact Prof. O. Jarrett; [email protected]) This group has close links with the Oncology theme, where tumour viruses are a major interest. Current interests include the pathogenesis of feline viral diseases (FIV, FeLV, FCoV) including the role of host immunity, viral sequence variation and receptor specificity. Efforts to develop and improve vaccines to these agents remain a high priority. A new initiative led to the discovery and characterisation of porcine endogenous retroviral families which pose a potential health hazard arising from xenotransplantation. Veterinary Microbiology & Public Health (Contact Prof. M. Roberts; [email protected]) The growth of this group has been a response to growing public health problems arising from food borne pathogens and the need to integrate molecular and more classical approaches to their identification and the study of their pathogenicity. The major focus of the group is the host-pathogen relationship and this approach is applied to the major zoonotic pathogens, Salmonella, E.coli O157, Campylobacter and the Transmissible Spongiform Encephalopathies (TSEs). The ultimate aim is to use the information gained from such studies to design more effective vaccines and agents to prevent or treat infections. Comparative Pathobiology (Contact: Prof. Jim Neil; [email protected]) Oncology (Contact Prof. R. Jarrett; [email protected]) Work under this theme has close links to Virology through its focus on the identification and characterisation of viruses as agents of cancer. The work of the LRF Virus Centre is devoted to the study of causal factors in human leukaemia and lymphoma, with particular emphasis on viral agents. A second programme has been initiated recently on the pathogenesis of Hodgkin's disease and the nature of the Reed-Sternberg (RS) cell, the presumptive malignant cell in this disease. This theme also includes the Papillomavirus Group, which has pioneered the development of vaccines to these agents. Their comparative research on human and animal papillomaviruses focuses on aspects of transcriptional control, cell transformation and protective immunity. These activities are complemented by the Molecular Oncology Laboratory, which is focused on the genetics and biology of haemopoietic malignancy. This work, which has its origins in comparative studies on feline leukaemia, exploits retroviral mutagenesis to identify oncogenes which are targeted in cancer and is developing novel models of neoplastic disease. Neuroscience (Contact Prof. I. Griffiths; [email protected]) The research of this group is directed at two main themes, myelination and the canine neurological disorder, chronic degenerative radiculomyelopathy (CDRM). The work on myelination focuses on the role of the major myelin proteolipid protein (Plp) gene in normal and diseased tissue and on using spontaneous mutations to reveal important aspects of myelination. This work has led to the recognition that PLP is essential to maintain axonal integrity in man and mouse. The work with CDRM is directed at identifying candidate causal genes. The nature and distribution of pathology is very similar to certain of the human hereditary spastic paraplegias, thus allowing a search for the canine orthologues of the causal genes. Reproductive Biology (Contact Prof. P. O’Shaughnessy; [email protected]) Research in this group is aimed primarily at study of the development and function of the hypothalamic-gonadal axis and its constituent parts. Studies on the gonads are focused on control mechanisms regulating fetal and pubertal development using transgenic and mutant mouse models which lack specific hormones or receptors. Interactions between the hypothalamus and the gonads are a second focus of this group and are primarily concerned with an understanding of the mechanisms by which gonadal steroids regulate hypothalamic- pituitary function. In addition, there are ongoing studies into the mechanisms of dominant follicle selection in the ruminant ovary. Animal Health (Contact: Prof. Stuart Reid; [email protected]) Population & Production Medicine (Contact Prof. J.Fitzpatrick; [email protected]) The population-based approach to research on animal disease encompasses the activities of two teams of researchers. Comparative Epidemiology and Informatics provides the environment for clinical researchers, epidemiologists, statisticians, information and computing scientists to apply their combined strengths to the quantitative assessment of disease risk, disease modelling and development of decision support systems. The Production Medicine group is focused on identifying the major genetic and immunogenetic determinants of resistance and susceptibility to disease and on product quality in production animals. The group has focused on parasitic disease and mastitis, and works collaboratively on these with the Roslin Institute (BBSRC), while developing an active and expanding tropical disease programme. Evidence-based Medicine & Diagnostics (Contact Prof. D.Eckersall; [email protected]) Built around the AVMA-accredited centre of clinical excellence, this group provides an environment for clinician-researchers as well as diagnostic researchers from clinical and pathology backgrounds to develop evidence-based medicine. The research is directed at the analysis of retrospective case series, case-based investigations, prospective clinical studies and the development of novel platforms, software and reagents for diagnostic instrumentation. The disease investigations and observations originating from this group are pivotal to the research success of the other groups within the Animal Health theme, with clinical investigations resulting in the production of commercial diagnostic kits and instruments. An example is the development of methods for the detection of acute phase protein as a marker of inflammation. Molecular Medicine & Therapeutics (Contact Prof. D.Bennett; [email protected]) With a focus on the development of clinical therapies and prophylaxis, this theme comprises 2 interlinked but distinct groups. The Molecular Therapeutics group undertakes research into the development and application of new treatment agents and strategies. One aspect is translational research focused on the developmental of gene-based delivery systems and therapies in veterinary target species. Current projects include the development of novel virus and DNA vectors for in vivo gene delivery and the characterisation of immunoregulatory cytokines and their potential application as vaccine adjuvants. In comparative investigations, key advances have been made in understanding and treatment of CNS-trypanosomiasis. Development of new therapeutics through basic and applied research is a core objective of the Veterinary Pharmacology Group. This group links with staff in other animal health groups in a targeted approach to pain management and animal welfare across species. .