The diagnosis and management of acute infections, especially as this relates to the prescription of antibiotics, is a health priority and serious concern in primary health care. Alastair Hay, in collaborations with the Universities of Cardiff, Nottingham, Oxford and Southampton, has secured funding for a project that runs through to 2018 and recruited over 24,000 patients to community based infection studies. This will be a resource in areas of population and health, epidemiology and modelling.

Mechanisms of colonisation and pathogenesis will be studied by epidemiological approaches and by structural and functional analysis at the molecular level. One focus will be polymicrobial infections involving the pathogenic fungus Candida albicans. Other research into the mechanisms of blood platelet activation by bacteria, colonisation by respiratory pathogens, and antibiotic resistance, focus on defining targets for interventions. Novel approaches such as solid state NMR as well as established crystallographic and microscopic techniques will underpin the development of a new generation of treatment strategies. Microbial resistance to antibiotics remains a critical concern around the country and the world and by combining the unique resources inherent in the combined medical, dental and veterinary schools, this issue is at the forefront of our research agenda.  

Parasites of all sizes adapt to the host environment. Investigators are advancing our understanding of the biology of the parasite and its evolution in many different environments. By combining transcriptomic and proteomic analysis of virus infections in cell lines, virologists in the School of Cellular and Molecular Medicine have been able to characterise the complex response of virus and host cells during co-infection of cells. The power of this approach is that it allows rapid, detailed and unbiased identification of therapeutic targets and it is facilitated by state of the art proteomic facilities. Nematodes are a focus of interest in the School of Biological Sciences and for these organisms the immune response of the host is an environmental challenge that influences evolutionary fitness. Parasites are also a crucial concern in veterinary medicine; studying and modelling such infections is a priority of Bristol Veterinary School.

A healthy immune system negotiates successfully with the infectious environment, providing effective resistance to dangerous infection and careful surveillance for developing cancer. When this balance is disturbed, different diseases develop. Autoimmune disease leads to immune attack directed towards healthy tissues, and current treatments use global immune suppression that leaves patients at risk of infection. Cancers resist immune attack by subverting normal mechanisms of tolerance and regulation. Research in this area focuses both on developing more focused therapies for autoimmunity, better understanding of how autoimmune disease progresses, and insight into mechanisms used by cancer to avoid immune attack. 

The one health agenda reflects our growing understanding that it is not sufficient to study human and veterinary infectious diseases in their own silos. The microbial ecology does not recognise such artificial boundaries and to fully understand its contribution to health and disease it is crucial to develop methodologies that can be broadly applied. Bristol has unique resources in this regard through the co-localisation in the University of the Bristol Veterinary School, the MRC Integrative Epidemiology Unit and the NIHR Health Protection Research Unit studying Evaluation of Interventions.

Work in this area is focussed on developing improved molecular methodology that can lead to increased diagnostic throughput at lower cost and with greater clarity of interpretation with regard to transmission. This area will also tackle assessing the impact of vaccination on normal microbial carriage and link carriage in humans with that in different animal populations.

Carrying out ‘hard to do’ epidemiological studies involving complex interventions or designs, multidisciplinary input or ‘hard to reach’ patient groups, such as those with particular infectious diseases, is a particular area of interest in Bristol, and a focus of work in the NIHR HPRU. Advances in understanding and manipulating immune function are limited presently by our ability to predict the outcome of immune responses in individuals. This reflects both the complexity of the biology but also the emergent properties of immune responses that are poorly reflected in common one gene/protein paradigms to studying immune function. The development of a computational biology framework applied to these problems, in bioinformatics, proteomics and imaging will lead to novel and important developments both in the basic understanding of disease processes and also the scope of interventions to promote human health. 

Collaborations spread widely both within and outside of the University.

Tuberculosis (TB) remains one of the deadliest infectious diseases, with 10 million new cases and 1.4 million deaths worldwide in 2019, and in the form of bovine TB is also a significant veterinary pathogen. Researchers across the University of Bristol are working to combat TB using a variety of approaches in an effort to improve understanding of disease transmission, detect cases more efficiently and develop new treatments that overcome the threat of antibiotic resistance.

Researchers in Bristol Veterinary School are applying modelling tools to surveillance and genomic data to investigate human and bovine disease transmission, the acquisition of zoonotic disease in those exposed to infected livestock, and the potential impacts of cattle vaccination. Interests in diagnosis (Schools of Cellular and Molecular Medicine, Physics and Chemistry) encompass nucleic-acid-based detection methodologies for human and animal disease, nanoparticle-based systems for human disease detection in resource-limited settings, and improving diagnosis of TB meningitis in children. Researchers in the School of Cellular and Molecular Medicine are also interested in host immune responses to TB infection. Projects seeking to develop better treatments for TB disease (Schools of Biochemistry, Chemistry and Cellular and Molecular Medicine) are using innovative approaches including new natural product and in silico drug discovery methods, together with drug combinations, to identify new treatments for drug resistant strains in particular.

Collaborations beyond Bristol include partner institutions in Kenya, South Africa and Thailand.