Research within the School of Cellular and Molecular Medicine
Research within the School of Cellular and Molecular Medicine is organised around three central themes: Cancer Biology, Infection and Immunity (incorporating bacteriology, immunology and virology) and Tissue Engineering and Stem Cell Therapies.
Bacteriology and Antimicrobial Resistance in CMM: the present
Bacteriology research within CMM encompasses the PIs Avison (bacterial molecular genetics and regulation of gene expression); Blocker (bacterial secretion systems involved in virulence); Finn (respiratory pathogens, vaccinology); Hill (human-pathogen interactions and vaccine discovery; mucosal pathogens) and Spencer (structure and mechanism of antibiotic resistance determinants). Antimicrobial resistance (AMR) is a focus of research in the Avison (characterisation of novel resistance mechanisms), Hill (infection and adaptation of resistant N. gonorrhoeae strains) and Spencer (structure, mechanism and inhibition of enzymes involved in resistance) groups while work in the Blocker laboratory includes countering AMR by exploiting secretion systems as targets for anti-virulence therapies. In addition the Finn, Hill and Blocker groups are all engaged in identifying targets for, and developing and evaluating, vaccines as a route to overcoming bacterial pathogens. Bacteriology is part of Infection and Immunity research, one of three major research areas in CMM, and which extends beyond the School to include researchers in other parts of the University of Bristol (UoB) including the Schools of Oral and Dental Sciences, Biochemistry, Veterinary Sciences and Social and Community Medicine.
AMR research in Bristol is a growing community that is cross-disciplinary and collaborative in nature. Relevant research activities elsewhere in UoB include identification and development of natural product antimicrobials (Schools of Chemistry, Biochemistry, Biological Sciences and Earth Sciences); investigation of resistance enzyme mechanisms (School of Chemistry); development of antimicrobial particles and surfaces (Schools of Oral and Dental Sciences, Physics and Chemistry, Centre for Nanoscience and Quantum Information) and mathematical modelling of resistance and resistance gene dissemination and the impacts of potential interventions (Schools of Veterinary Sciences, Engineering Mathematics and Social and Community Medicine). These cross-disciplinary activities have received a major boost with a successful recent bid for Engineering and Physical Sciences Research Council (EPSRC) “Bridging the Gaps” funding to create a network “BristolBridge” that co-ordinates and promotes networking between researchers in the biomedical and physical sciences and will provide pump-priming funding for innovative cross-disciplinary research projects with a specific focus on AMR. In CMM Spencer and Avison are leading BristolBridge activities in the areas of small molecule therapeutics development and impact, respectively. AMR research also benefits from investment in and improvements to relevant research infrastructure that includes the BlueCrystal supercomputer; state-of-the-art facilities for LC-MS/MS proteomics; a comprehensive suite of imaging instrumentation for light and electron microscopy (Wolfson Bioimaging Facility) and structural biology instrumentation including a cryo-enhanced 600MHz NMR instrument and automated facilities for protein crystallization (Biotechnology and Biological Sciences Research Council (BBSRC) ALERT14 equipment funding). Automated facilities for molecular biology are also available in the BioSuite, part of the joint BBSRC/EPSRC funded BrisSynBio initiative.
Beyond UoB AMR research in CMM also benefits from local collaborations elsewhere in Bristol and the surrounding region. Active links already exist between CMM researchers and clinical microbiologists at both the University of Bristol and the North Bristol NHS Trusts, in particular through the Bristol Centre for Antimicrobial Research and Evaluation (BCARE) led by Prof Alasdair MacGowan at Southmead hospital. UoB is also part of the GW4 alliance of research intensive universities in the South West of England and Wales, which exists to promote and strengthen research links between these institutions. Active collaborations currently exist between AMR researchers in CMM and the University of Cardiff, and AMR researchers elsewhere in UoB with the University of Exeter.
AMR research at Bristol offers exciting opportunities for interdisciplinary collaboration in AMR research. We seek to appoint an individual who can bring an active research programme in AMR that complements our existing strengths, exploits opportunities for new collaborations and maintains and extends the reputation of Bristol as an institution at the forefront of UK research activities in AMR.
Virology research in CMM: the present
Virology research within CMM currently centres around the research activities of three PIs (Yamauchi, recently recruited from Zurich, Davidson and Matthews) and focuses on the study of the replication and pathogenesis of viruses of medical (influenza virus, dengue, emerging coronaviruses, adenovirus) and veterinary (feline coronavirus) importance. The emphasis of the research is on the use of high throughput “omics” techniques to investigate the viral-host interface, in particular, the ways in which viruses modulate the host immune response to cause disease or facilitate zoonotic transmission. The virologists in CMM interact with others in the School and more widely in collaborative studies aimed at; identifying novel viruses in clinical and veterinary samples; understanding the combined interaction of viruses and other microbes on human health and understanding the immune response to infection.
In recent years, virology research in CMM has moved from a virus-centric approach to a more systems-level view of the interaction between virus and host. In the last School review, one of the research aims was to “Expand our research programmes to take full advantage of new technologies in the biomedical sciences”. The virology researchers embraced this vision, taking full advantages of the state-of-the-art transcriptomics, proteomics and supercomputing facilities at the University of Bristol (UoB). Not only have the virologists used advanced “omics” approaches to conduct novel studies on the host response to the viruses they study, but importantly they have pioneered a novel bioinformatic approach (Matthews, Proteomics Informed by Transcriptomics (PIT)) to study the host response to infection in the absence of an available full genome sequence. This approach has the potential to be transformational in the study of interactions between microbes and non-model hosts such as those encountered in the study of emerging viral diseases. These include adenovirus, Ebola virus, Hendra virus, Nelson Bay virus, coronaviruses and dengue virus. All these studies have a strong emphasis on the molecular basis of host cell interactions. A spin-off from these investigations has been the development of bioinformatics expertise amongst the virologists which is an asset not only for CMM but also the faculty and UoB as a whole. Most recently Bristol virologists have been awarded a substantial grant from the BBSRC to study MERS-CoV using integrated ‘Omics based approaches in human, bat and camel cell lines.
Virology is taught in a number of undergraduate and postgraduate units and in the preclinical years of medicine and dentistry. Undergraduate students may also enrol in a degree in Virology and Immunology.
The virologists are committed to pursuing their “omics” approach to take a systems-level view of the host-pathogen interface. This approach is ideally suited for increasing our understanding of disease pathogenesis, identifying cellular targets against which anti-viral strategies can be developed, characterising the immune response elicited by an effective vaccine and understanding how either novel viruses emerge into the host population or existing viruses interact with other microbes to cause disease. The “omics” expertise we have developed has already fostered a number of clinical and veterinary collaborations which we aim to increase in the future. There is also much potential within the university to forge cross-faculty collaborations in the field of synthetic biology which has much promise for the future. To complement and build on the existing virology expertise, there is a need to recruit a virology academic who has a demonstrated track record in the study of viral diseases of medical or veterinary importance. The individual would be able to contribute to the teaching of virology and build on the current strengths in virology with the other PIs, to develop a distinct identity for virology in Bristol.
Immunology research in CMM: the present
Immunology continues to have considerable strength and depth and centres around the research activities of six PIs (Dick, Finn, Morgan, Nicholson, Wood and Wuelfing). Immunologists focus on autoimmune diseases, molecular and tumour immunology, inflammation and the immunology of infectious diseases. Expertise spans from fundamental immunology, defining the molecular and cellular basis of these diseases, through to clinical practice, i.e. the treatment of autoimmune conditions and infectious diseases. The field of molecular immunology was recently strengthened by the addition of Prof Linda Wooldridge, Chair in Veterinary Sciences and based in CMM, who brings novel expertise in the molecular basis for MHC-T-cell receptor interactions.
Immunology represents one of the principal translational areas of the school which is recognised within the University and Bristol generally. Dick, Lee and Nicholson study the immunology of uveitis in experimental models and man, and evaluate immunotherapeutic approaches for treatment of this disease in the clinic. Finn and Heyderman (international collaborator) study the immune response to various mucosal pathogens and the translation of this knowledge to development of improved vaccines for treatment of these diseases, much of their work being conducted through fieldwork and clinical trials.
Two new members of the Infection and Immunity theme have recently joined CMM and provide links with the Cancer theme. Dr Eugenia Piddini was recruited from Cambridge University and has recently secured a Wellcome Trust Senior Fellowship. Along with Prof Will Wood, the School now has two Wellcome Trust Senior Fellows. Dr Marc Amoyel was recruited from New York University under the University of Bristol EBI scheme and has now been awarded an MRC Career Development Fellowship. Dr. Piddini and Dr Amoyel join Prof Will Wood in the use of Drosophila as a model organism and work on cell competition in the microenvironment.
The School is currently recruiting three new posts in Infection and Immunity.
Cancer Research in CMM: the present
Cancer research within CMM has until recently been centred on the research activities of five PIs (Brown, Malik, Paraskeva, Roberts and Williams) with expertise in colorectal tumour biology and chemoprevention, childhood cancers (with a focus on WT1), genetic and epigenetic regulation in cancer. Profs Paraskeva and Williams are actively involved in study of the mechanism of action of aspirin as a cancer preventive/treatment in colorectal carcinoma, including clinical trials based in Bristol.
The research of Drs Brown and Malik, and Prof Roberts concerns paediatric tumours and particularly Wilms’ tumour and Neuroblastoma. The Wilms’ tumour 1 protein WT1 is a focal point and the groups complement each other to study the biochemistry, genetics and cancer biology of WT1. With collaborators at the University of Bath [Ward] and the University of the West of England (UWE) [Ladomery] this now makes Bristol/SW an international hub of WT1 research.
Expertise in genome organisation, gene regulation and cancer has been further boosted by the appointment of two new academic staff in cancer biology, Abderrahmane Kaidi and Abdelkader Essafi. They have come to CMM attracted by the possibilities of establishing their groups in this developing centre of excellence in WT1 and genome regulation research. The school has a strong sense of direction and common purpose within the Faculty Cancer theme (collaborations with Martin) and building on strengths in basic research, we are working towards increasing clinical partnership: bringing together researchers [UoB and UWE] with clinical partners involved in both primary and secondary cancer care. A further opportunity comes from the strong desire for closer collaborative working within the University Hospitals Bristol [UHB] which has three strategic themes for R&D. These are Cancer, Cardiovascular and Children. Our interests in adult and childhood cancers therefore directly map to these.
Tissue Engineering and Stem Cell Therapies in CMM: the present
Tissue Engineering and Stem Cell Therapies (Blair, Kafienah, Perriman, Steward, Uney, Wong) is a relatively new theme within the School of CMM. The on-going plan for this theme was to bring different research groups together in one laboratory to provide clear critical mass for regenerative medicine. This has been achieved with the establishment of the Regenerative Laboratory housed in the Biomedical School Building.
The Regenerative Medicine Laboratory as well as the Adult Stem Cell Group includes:
- The Embryonic Stem Cells group (PI: Dr Wael Kafienah).
- The Cancer Stem Cells Groups (PI: Dr Allison Blair).
- The Neuroregeneration group (PIs: Professor James Uney and Dr Liang-Fong Wong).
- The Materials Chemistry group (PI: Dr Adam Perriman).
This theme, as well as the school generally, has been strengthened by the recruitment of EPSRC Senior Fellow/Senior Lecturer, Dr Perriman (from Chemistry, Bristol) who works in the field of nanomaterials chemistry. He brings a completely new type of science into CMM/Medical Sciences and this will enable many researchers to collaborate with him on exciting new projects. His move from Chemistry to CMM strengthens the ties between these Schools and will lead to further, wider collaborations in the future. More recently, the theme has been enhanced by the appointment of Rafael Carazo Salas from Cambridge University. Professor Carazo Salas works in the development of cutting edge image-based screens that will be applied to stem cell research.