RA5a: Structure,environment and staffing policy
1. Introduction. Our research encompasses basic and applied biomedical and veterinary sciences. It ranges from molecular sciences to clinical sciences and comparative medicine. This is a broader remit than is seen in most single-discipline biological sciences Departments, and is a strength which enhances our research. We aim to be internationally competitive in research, to foster collaborations with academia and industry and to ensure that our undergraduate and postgraduate teaching and clinical work benefit from research excellence.
2. Organisation. The Director of Research co-ordinates the Department’s research activities. These are sub-divided into 5 key areas: Neurology, Infection and Immunity, Genetics, Clinical Sciences and Animal Welfare. Each area is overseen by a Professor or Senior Faculty member, responsible for co-ordinating and facilitating the activities of their Units. Each area is further sub-divided into research groups each headed by a Principal Investigator (PI). PIs can be Professors, Readers, University Lecturers or Research Fellows. They are responsible for obtaining independent research funding. Most groups employ one or more post-docs and/or technicians and include graduate students. Interdisciplinary collaboration between groups is strongly encouraged.
3. Research activities and main achievements (Many others are involved in the research but only those listed on RA1 are identified below. Total numbers of post-docs and graduate students (past & present) involved during the research period are given)
3.1. Neurology. (Blakemore, Crang, Franklin, Jeffery, plus 8 postdocs and 7 graduate students)
The Department’s research in neurology led by Blakemore and Franklin has been starred in all RAEs. The research focus remains development and evaluation of strategies for enhancing repair in the nervous system with particular emphasis on understanding the cellular mechanisms that underlie remyelination in the CNS. Notable advances have been: the first demonstration that glial cell transplantation can lead to functional recovery from demyelinating lesions (Jeffery), studies on the role of growth factors in remyelination (Franklin), examining the origin of the cells responsible for remyelination (Crang, Blakemore), the behaviour of transplanted Schwann cells and their derivation from multipotent precursors (Crang, Franklin, Blakemore), transplantation of olfactory glia (Franklin) and porcine multipotent glial cells (Blakemore). Unique insights have been gained into how far endogenous and transplanted oligodendrocyte progenitors can be recruited to progenitor depleted areas of demyelination (Franklin, Blakemore). The discovery of the remyelinating potential of human olfactory ensheathing cells (Franklin) is novel and unexpected opening up new clinical and therapeutic applications.
3.2. Infection and immunity. (Awan, Blacklaws, Bryant, Field, Holmes, Lachmann, Lloyd, Maskell, Mastroeni, McConnell, Preston, Slater, Tiley, 16 post-docs and 20 graduate students).
Infection and immunity was starred in the last RAE. Much of the research in this area is new to the Department being initiated by new appointments after 1994 (Blacklaws, McConnell, Tiley) and continuing during 1996-2000 with the appointments of Maskell (1996), Mastroeni (1999) and several independent Research Fellows awarded in open competition (Bryant, Slater and 2 others). The main achievements have been to define the mechanisms used by bacterial and viral pathogens to infect and persist in their hosts and immunity to these pathogens.
3.2.1. Bacterial pathogenesis. Genes required for LPS biosynthesis in a number of gram negative bacteria have been identified (Maskell) and a defined series of stable mutants in Bordetella and Salmonella created to explore the biochemistry of LPS and its role in infection (Preston). Novel genetic techniques are being used to perform signature-tagged mutagenesis in Streptococci to define virulence factors for pigs and horses (Slater). Functional genomics and microarray techniques are being used to study host pathogen interactions in food borne infections of farm animal hosts by Salmonella, Campylobacter and E. coli O157 (Maskell). A novel gene inhibition strategy is being developed both as a functional genomics tool and as a method for attenuating pathogenic bacteria (Tiley). Bryant has defined a previously unrecognised role for Lipocortin 1 in the ERK-MAP kinase signalling pathways, thus elucidating key steps in LPS-induced endotoxaemia.
3.2.2. Immunity to infection. Our research on the ruminant lentivirus, Maedi-Visna (MVV) has provided a unique animal model for studying pathogenesis and immunity of a macrophage-tropic lentivirus. This is a long-established research programme (Blacklaws and McConnell). We have defined for the first time the role of dendritic cells and T cells in lentivirus replication in vivo, and developed and evaluated MVV recombinant proteins for MVV diagnostics. The chromosomal location of the MVV receptor has been identified and found to be different from the chemokine receptors used by HIV and FIV (Tiley). A novel series of influenza virus fusion inhibitors has been studied by Tiley. The role of IgA and Fca receptors in immune complex formation and models for the treatment of immune complex disease with recombinant DNAse have been published. A new streptococcal complement inhibitor has been discovered and patented. (Lachmann). The molecular and genetic basis of some of the bacterial evasion strategies for Salmonella infection have been elucidated (Mastroeni). Discoveries in the herpesvirus group led by Field (Awan, Field, Slater) include identification of EHV-induced neuronal latency and focal retinopathy in the horse; new insights into the action of the antivirals in HSV, and creation of a novel deletion mutant of EHV for pathogenesis studies. Monoclonal antibodies to equine immunoglobulins have been made and used in defining equine immunoglobulins and Fc receptors and organisation of equine immunoglobulin genes (Holmes). New work on the peripheral pathogenesis of scrapie (McConnell) has begun and Lloyd’s research on the biology and control programmes of echinococcosisis (with international collaboration) is being extended to Hexamitosis.
3.3. Veterinary genetics (Ferguson-Smith, Rens, Sargan, Skelly, Yang, 2 postdocs and 7 graduate students).
Research on inherited diseases in the dog and cat is recent, starting from the appointment of Sargan in 1994 and establishment of a comparative cytogenetics group in 1998 (Ferguson-Smith, Yang, Rens). This has already led to significant findings in veterinary and comparative molecular cytogenetics. Sargan has identified the gene mutations for the different forms of canine progressive retinal atrophy (PRA) in different breeds of dogs, and the genetic basis of fucosidosis and pyruvate kinase deficiencies has been established (Skelly, Herrtage, Sargan). DNA diagnostics based on these discoveries have been developed. New canine mapping data has allowed us to start using linkage analysis in investigations of several forms of PRA. A clinical genetics service has been started. We have published complete comparative maps of dog, cat, fox, and human genomes, and canine linkage groups, syntenic groups and radiation hybrid groups have been tied to chromosomes, allowing judgement of the completeness of these maps (Yang, Sargan, Ferguson-Smith). Technologies for chromosome sorting and fluorescence in-situ hybridisation have established new knowledge of chromosome evolution in carnivores, primates and marsupials (Yang, Ferguson-Smith, Rens). Novel methods for checking purity in sex-sorted spermatozoa have been published, patented and utilised in sperm sexing (Rens). These build on previous work using high resolution and efficient DNA analysis of X and Y chromosome bearing sperm which allowed for the first time a high throughput sorting of X and Y sperm for sex selection in cattle.
3.4. Clinical sciences (Allen, Cockcroft, Davies, Dobson, Evans, Heath, Herrtage, Holdstock, Holmes, Jeffcott, Jeffery, Taylor, Skelly, 2 postdocs and 12 graduate students).
Integration of clinical and basic research expertise is allowing new developments in clinical science. In small animal clinical science this is best exemplified in clinical genetics. We have been the first to describe a new form of ciliary dyskinesia in the Newfoundland dog breed and a DNA microsattelite marker for copper toxicosis in the Bedlington terrier breed (Herrtage, Skelly, Sargan). Breed specific sarcomas, lymphomas, melanomas and malignant histiocytosis have all been characterised and new treatment regimes evaluated (Dobson). A cytogenetic study of chromosome abnormalities in these breed-specific cancers has started (Dobson, Sargan). Immunological markers have defined canine histiocytomas as malignancies of the dendritic cell lineage. (Dobson, McConnell). Jeffrey’s expertise on basic neurology has application to spinal cord injuries in dogs.
In Equine Sciences, linkage of basic research on the cell biology of equine chondrocytes and the role of cysteine proteinases in endochondral ossification and osteoclast activity (Jeffcott, Davies) has led to new knowledge on the role of Cathepsin B and D in cartilage remodelling and an improved understanding of developmental abnormalities in equine dyschondroplasia (Jeffcott). Novel studies which have led to the identification of ADP receptors on human platelets and the role of ADP in endotoxin activation of equine platelets have direct application to therapy of equine thromboembolic diseases (Evans, Heath). Allen leads an internationally recognised equine reproduction group whose discoveries include the first viable hybrid ever to be produced between Old World and New World Camelids, new understanding of the materno-fetal immunological interactions in horse/donkey pregnancies and role of growth factors in endometrial development in the horse. Taylor has investigated the endocrine and metabolic responses in anaesthesia and shown that volatile agent anaesthesia causes cardiovascular depression and a greater stress response leading to more anaesthetic deaths. Holdstock’s research is now focussed mainly on intrauterine growth retardation on organogenesis and increased mortality and morbidity in the foal. A new equine disease - Fell pony syndrome - characterised by anaemia and immunodeficiency has been discovered (Holmes).
The Farm Animal Group has focussed strongly on evidence-based medicine and development of pattern-matching models for diagnosis. Current research projects include development of a pattern-matching system for differential diagnosis in BSE and scrapie (Cockcroft).
3.5. Animal welfare, behaviour and nutrition. (Bradshaw, Broom, Chiy, Miller, Podberscek, Phillips, 9 postdocs and 12 graduate students).
The group has been a world pioneer in animal welfare research for 14 years. Key concepts such as welfare, stress, needs, feelings and awareness have been clarified and the assessment methods developed are now used in many countries. Major papers on housed sows show how confinement leads to bone weakness, abnormal behaviour is linked to opioid activity in the brain, and crushing of piglets by sows can be prevented by pen design (Broom, Bradshaw). Cattle lameness has been shown to be a consequence of hoof quality, and social variables have been shown to be modified by physical conditions (Broom, Phillips). Papers on welfare of pigs and sheep during transport evaluate the importance of genotype, previous experience, loading procedures, stocking densities, vehicle movement, temperature and humidity. Some EU and UK legal requirements have been significantly influenced by housing and transport work. Studies on enriching the environment of rats and cats have led to better codes of practice (Broom). Podberscek has examined how aggression and other problems in dogs depend on genetics, owner personality and treatment. There have been significant studies on visual perception, olfaction and rhythms. Studies on animal nutrition have focussed on the effects of sodium fertiliser and heavy metals on disease susceptibility in ruminants; lameness in cattle, rumen metabolism and effects of n-6 and n-3 essential fatty acids and vitamin E on tissue composition; oxidative stability and heart function in pigs; effects of processing on protein structural changes and digestibility of fish feeds (Phillips, Chiy, Miller). In collaboration with 22 laboratories from 13 different countries throughout the world, new methodologies for the analysis of Iodine Value in fish oil, and solubility in pepsin of fish meals, have been adopted for use in the world trade in fish oil and fish meal (Miller).
4. Promotion and Management of Research. The Director of Research (McConnell) is responsible for promoting and managing the research of the School. A Research Board, comprising senior Faculty members and research investigators representative of each research area, reviews broad strategic areas for research and longer-term research initiatives. The Board assists new appointees in identifying new research opportunities, informs and plans research initiatives, assists with preparation of research grant submissions, advises on external research contacts and generally fosters research developments and sponsorship. Research mentoring is reinforced within the research groups. Each group has several PIs and a research infrastructure into which new staff can be readily assimilated and their research programmes supported financially and intellectually. Each research area has journal clubs and holds weekly meetings to review research in progress. The Department has a Research Club with weekly presentations by senior and junior research staff and invited external speakers. Interdisciplinary interactions are promoted through joint research seminars, collaborative research grant proposals, open-plan laboratories and shared research facilities.
5. Graduate education and training. Postgraduate degrees by research include PhD, MSc, MPhil and a newly established Vet.MD. A committee overviews research training and facilities for graduate students within the Department, while the Cambridge University Graduate School in Biological, Clinical and Veterinary Sciences, of which Sargan is Assistant Chairman, was established to increase the educational breadth of research degrees and ensure an even level of supervisory best practice. It is responsible for developing recruitment and careers advice for graduate students, supervisory arrangements, assessment of research training, teaching of core laboratory and generic scientific and presentational skills, computing and legislative/safety requirements. Progress has been reflected in support from the outside funding agencies. The Department now obtains Quota and Research Council studentships and is part of the 4-year Wellcome Trust-supported PhD Programme in Infection and Immunity, to which it contributes teaching modules and PhD supervision (Blakemore, Maskell, Mastroeni, McConnell). We also obtain research studentships from charities and industry-related bodies (e.g. British Egg Marketing Trust, Astra Zeneca, and SKB Glaxo-Wellcome). The Department has trained 54 graduate students during the period, some registered through other Faculties. Standards are monitored through the use of progress logs and annual formal assessment of graduate students. Clinical PhD students on 4 or 5 year programmes join the established clinical Residency training programmes run by White, Dobson and Herrtage. For the last 6 years Broom and colleagues have run an international course on Animal Welfare for veterinary surgeons.
The Department has taken a lead at international level in promoting research awareness in clinical veterinary students by creating a highly successful 5-year programme of 9-week Summer Schools funded by the Wellcome Trust (£311K) and directed by Sargan. Our veterinary undergraduates are also exposed to research through the compulsory Part II year (equivalent to an intercalated Honours year) with research projects in any laboratory in Cambridge, and then through 4th Year Projects and 9-week Final-Year Electives which can be spent in research laboratories in Cambridge or elsewhere.
6. Research infrastructure. The Department’s buildings underwent major reconstruction and refurbishment just before the start of the current RAE period and not included in RA4. Phase 1 of the Centre for Veterinary Science, funded by the Wellcome Trust and the University, provided 840m2 of open-plan and containment laboratories. Investment in research facilities continued over the current period. Phase II of the Cancer Therapy Unit opened (£250K, Pet Plan) with high-voltage radiotherapeutic facilities and imaging technology. Category II containment laboratories for bacteriology research were funded (560m2, £700K, Smith-Kline Beecham and University; £401K, HEFCE/MAFF), also cell culture and cytogenetics labs, a radioisotope suite (300m2, £375K Wellcome Trust), a Video Conferencing suite for the £350K Joint Residency Training Programme in Pathology with the Royal Veterinary College (Smith-Kline Beecham). Recently completed is a new post-mortem room used by all research groups (£2.1m, HEFCE), a new University Farm Dairy Unit used by the welfare and large animal clinical groups (£1.2m, HEFCE). Construction is about to start on an Equine Diagnostic Unit (£750K, Home of Rest for Horses) to complement the Equine Surgical Suite completed in 1998 (£650K Home of Rest for Horses).
Throughout the Department there are now excellent facilities for cellular and molecular sciences including 2 Becton Dickinson Flow Cytometers, 2 electron microscopes, automated DNA sequencing, a powerful 2-laser FACS for chromosome sorting, 3 dedicated u.v. microscopes each with specialist peripherals and software for different methods of fluorescence image acquisition and analysis. Individual research groups mainly fund IT facilities from grants, but the Department provides computing facilities for new HEFCE-funded staff, and contributes £79K p.a. at current costs to the costs of the University’s Computing Service. To accommodate the high level of traffic (for electronic journals, bibliographic, genomic proteomic databases and bioinformatics, email and on-line accounting) we have established a fast switched ethernet infrastructure linking researchers in all parts of the Department, and provided a 30-seat computer room for undergraduates and postgraduate students (£25K Lee Foundation £48K University). A computer officer post has been established to support these IT developments. Research facilities in other parts of Cambridge University and related Institutes which we use in our research programmes include the Multimaging Centre (Anatomy), cell sorting (Clinical School), MRI imaging (Smith-Kline) and genome sequencing at the Sanger Centre. Here we have two jointly funded research programmes on sequencing the genomes of Campylobacter and S.equi – (Slater, Maskell, Preston). For Clinical Sciences, CAMVET funds (£1.5m) and clinical fee income are being used to develop new small animal surgical facilities which will be essential for clinical neurology and oncology.
7. Use of funding to support research and significant external awards. The University spends, in support of the Department’s research, more than is received from HEFCE on account of the Department’s research. The largest proportion is spent on academic and support staff salaries attributable to research, followed by expenditure on premises and core equipment used predominantly for research activity. The University supports each new Lectureship with a setting up allowance of £17K for individual research. Significant external research grants are held by groups in neurology, infection and immunity and animal welfare. We have won 5 competitive Wellcome Trust Research Fellowships (Allen, Blacklaws, Bryant, Franklin, Slater) and 59 research grants in open competition to support the research in Neurology and Infection and Immunity. The Neurology group is a partner in the MRC Co-op in Brain Repair and has access to the Centre for Brain Repair (£1.5m MRC Co-op Award for Neurology). EU, MAFF and other grants for welfare and nutrition research have totalled over £800K (Broom, Miller, Phillips). The Wellcome Trust is funding a Programme Grant (Maskell) and several long-term Research fellowships (Franklin - Proleptic Lectureship), Bryant (Advanced Training Scholarship), Slater (Research Leave Fellowship). There has been a particular focus on research programmes in food-borne infectious diseases and Maskell has won major funding from MAFF and BBSRC. This comprises a MAFF Senior Fellowship in Veterinary Microbiology (£1.3million, Maskell) and a BBSRC 5-year research programme on salmonella immunity (£696K to McConnell and Maskell) together with the Institute of Animal Health (£755K). Significant Wellcome Trust funding (£2.4 million) has been won in six separate project grants (Blacklaws and McConnell, Mastroeni, Maskell, Franklin, Blakemore, Tiley). A collaboration has been funded with the Sanger Centre to sequence the S.equi genome (£250K, Home of Rest for Horses). A Veterinary Epidemiology and Informatics (EPI) Unit involving 5 of the academic staff has been set up (£500K, Tetra Laval). Partnership awards are held with Smith-Kline Beecham/MRC (£623K, Lachmann) and (£239K, Arrow Therapeutics Ltd.). The Thoroughbred Breeders Association supports the Equine Fertility Unit (£800K per annum, Allen). £150K of clinical income is being used to develop new small animal hospital facilities and £20K per annum of clinical income is contributed annually to our University equipment allocation. Research spending continues to rise. The August-December 2000 expenditure figures in RA4 under-state research spending so far this year by at least £500K. This is due to the introduction of a new accounts system by the University which has delayed the recording of financial expenditure.
8. Arrangements supporting interdisciplinary and collaborative research. Cambridge is a fertile environment for research collaborations. The Neurology Unit is an integral part of the multidisciplinary Cambridge Centre for Brain Repair. There are research links with the Clinical School in lentiviruses, herpesviruses and gene therapy; the Department of Pathology in infection and immunity, oncology and clinical genetics; and the Babraham Institute in equine reproduction and animal welfare. Notable interdisciplinary research programmes are in molecular biology of influenza virus replication (Tiley and Digard - Pathology, MRC project grant), orthopaedics/rheumatology (Davies, Jeffcott and Clinical School), lentiviral vectors (Franklin and Lever - Clinical School). In TSE research (McConnell, Brown and others – Biochemistry) have jointly established the Cambridge Prion Consortium. In Infection and Immunity the MAFF Fellowship (Maskell) involves collaboration with Imperial College, and the BBSRC Programme Grant in Salmonella immunity (McConnell, Maskell) links us with the Institute for Animal Health. We have two funded collaborations with the Wellcome Trust Genome Centre (Slater, Maskell, Preston) for bacterial pathogen genome sequencing for S. equi and the three main Bordetella species. An Equine Orthopaedic Research Group (EORG) was established in 1997 to co-ordinate the existing collaborations with Strangeways Research Laboratory, the Departments of Anatomy, Rheumatology and Orthopaedic Surgery in research in equine dyschondroplasia. One staff member from Strangeways (Davies) relocated to the veterinary school to support the EORG. Sargan’s eye research is linked with the Institute of Ophthalmology, London. There are funded collaborations with eleven animal welfare and two nutrition laboratories throughout the EU, under the various schemes funded by the EU. Major examples of collaborations with industry include: Neurology - collaborations with SKB in neuropathology, with ReNeuron in evaluation of neural stem cells (Blakemore), with Cambridge Neuroscience in growth factors in repair, and with partners in two EC Framework 5 programmes (Franklin). Infection and Immunity – novel antimicrobials (Maskell and Arrow Therapeutics Ltd.); development of antivirals for herpesviruses (Field and Glaxo-Wellcome, Smith-Kline Beecham, Medivir); bacterial complement inhibitors (Lachmann and Adprotech, Patented). Genetics - development of chromosome paints and optical technologies for M-FISH and *FISH by the veterinary cytogenetics group (Ferguson-Smith and CAMBIO); new technology for X/Y sperm cell identification (Rens and Leica); development of herpes–amplicon viral vectors for gene therapy (Sargan and Cantab Pharmaceuticals - patent filed); studies of welfare aspects of farm animal behaviour and disease (Broom and Pfizer).
9. Staffing policy. As a clinical Department the requirement to teach a broad clinical curriculum and deliver small-group clinical teaching constrains our ability to select staff purely on research credentials. This is particularly acute problem for this veterinary school since preclinical and some paraclinical appointments at Cambridge are within the major biological sciences departments. We are overcoming these difficulties in several ways. Firstly, through the creation of specialist posts (University Surgeon: University Pathologist, University Physician) which are full-time clinical teaching and service posts. Our Resident training posts also contribute to clinical teaching and Hospital work. Appointments to these posts relieve pressure on clinical academic posts to offer release time for research. Secondly, we are creating ‘bridging Lectureships’ which have a 50% clinical:50% research split. So far we have established three (Jeffery - neurology, Skelly - clinical genetics, Villiers - diagnostic pathology/oncology). Thirdly, in teaching posts where there is no diagnostic requirement, we recruit non-veterinarians with research promise and established track record (e.g. Mastroeni in Microbiology; Tiley in virology). We encourage clinical staff to apply for Wellcome Trust Research Leave Fellowships (Slater) and use clinical income to support clinical service positions to provide release time for research (e.g. Taylor in anaesthesia). HEFCE-funded established posts are supplemented by Wellcome Trust Research Fellowships (Bryant, Preston and one category B staff). Retention and recruitment of staff in Cambridge has been addressed by the creation of a Senior Lectureship grade, and in the first year of this the Department secured 10 promotions.
Copyright 2002 - HEFCE, SHEFC, ELWa, DEL
Last updated 17 October 2003