Infection, immunity and inflammation

Antibiotic-resistant infections are one of the leading threats to human health and modern medicine. Both the WHO and national governments have stated that urgent measures are needed to avert the crisis we face. The antibiotic-resistant pathogens research group runs a programme for the discovery of bacteriocins, antimicrobial peptides produced by bacteria. These have an excellent potential for development into the next generation of powerful antibiotics to treat and prevent drug-resistant infections and are being developed commercially through UoP spin-out company Amprologix.

The group also studies pathogens that cause drug resistant infections and has a particular focus on urinary tract infections which causes an enormous levels of antibiotic prescription. The group’s significant expertise in the analysis of the genetic relationships of these bacteria, helps them understand the factors that lead to the development of antibiotic resistance and the spread of these infections.

( Professor Mathew Upton , Dr Philip Warburton ).

One area Plymouth researchers are engaging in is the discovery of novel compounds with anti-microbial activity from more "unusual" environments. For example, Dr Lee Hutt has been conducting research into microbiological diversity of the Roman baths in Bath – the UKs only ‘warm’ hot spring. Elsewhere Lee is working to identify novel therapeutics/prophylactic treatments for Giardiasis – recognised by the World Health Organisation as one of the world’s most neglected diseases where there is also evidence of anti-microbial resistance.

Other recent successes include some very promising discoveries from the South Africa-UK Antibiotic Drug Discovery Hub (a 3-year, £1.4m project led by Professor Upton on the UK side and Professor Rosie Dorrington at Rhodes University in South Africa). These discoveries include exciting novel compounds with antifungal and antibacterial activity that are being progressed for evaluation as future antimicrobial therapies for serious and difficult to treat infections.

The Group utilises novel cell lines and 3D cell cultures to investigate the immune / inflammatory response to endotoxin and other bacterial molecules, with application in the environmental detection and human health effects of endotoxins and pollutants, the identification of novel anti-inflammatory therapies and sepsis.

The patented endotoxin detection assays developed through the course of this research are being developed commercially through the UoP spin-out company MolEndoTech.

Professor Simon Jackson

The Hepatology Research Group uses state of the art laboratory facilities based in the Derriford Research Facility and the world class clinical research strengths of the Faculty of Health and Plymouth Hospitals NHS Trust. We work in unison with the South West Liver Unit, at Plymouth Hospitals NHS Trust, providing a full range and secondary, tertiary and community Hepatology services to the South West region, including assessment for liver transplantation, TIPS and liver cancer therapy. The research team run several commercially sponsored clinical trials in hepatitis C therapy, non-alcoholic steatohepatitis (NASH), primary biliary cholangiopathy (PBC), alcoholic liver disease and liver failure amongst others, through the clinical research facilities of The Lind Research Centre at Derriford Hospital.

The broad themes of the hepatology research group are:

In 2020, the group opened an observational clinical trial at UHP to test biomarkers of outcome of patients hospitalised with COVID-19. Other research highlights include the identification, using next generation sequencing, of six genes expressed in the liver that had rare genetic signatures in the small number of people who appear resistant to the Hepatitis C Virus.

More recent studies have looked at the health-related impact of COVID-19 and its impact on overall mental health among a range of individuals with existing long-term health conditions ( Bacon ).

Meanwhile the Dietetics, Human Nutrition and Health have developed a COVID-19 recovery knowledge hub to support patients who have developed long-term symptoms after catching Covid.

Macrophages are at the forefront of immune defence against pathogens and tumours. They exhibit a degree of functional plasticity which, when dysregulated, contribute to inflammatory pathology and cancer. Our research centres on the role of mucosal macrophages in homeostasis and pathology; with the specific aim of manipulation of plasticity and functional activation/suppression as a future cell-based therapeutic regimen in the treatment of gut diseases (Crohn’s disease, ulcerative colitis, colorectal cancer) and oral mucosal diseases (chronic periodontitis and oral squamous cell carcinoma).

( Dr Andrew Foey , Dr Gyorgy Fejer )

A recent example of this work has been a project led by Fejer which was funded by the National Centre for the Replacement Refinement and Reduction of Animals in Research. The research looked at establishing novel macrophage cell lines to replace the genetically modified mice used to study bacterial pathogenesis (the process by which bacteria leads to disease).

By 2050 it is estimated that 10 million people worldwide will die as a result of being infected with drug-resistant bacteria. Bacteria which were previously susceptible to antibiotic treatment have evolved to develop resistance to commonly used antibiotics, rendering them ineffective to combat infection. Now there are fewer antibiotics available to treat patients with certain infections. Hence, there is a global drive not only to discover new antibiotics to combat these bacteria but also to develop new types of diagnostics that can help diagnose infection at the point of care.This research focuses on designing low cost, rapid (five minutes), point of care nucleic acid-based biosensor assays for detection of AMR resistance genes and other pathogens that work within minutes from sample to result.

( Dr Tina Joshi )

Recent successes include a fruitful collaboration with Modus Laboratories on Anaerobic Oral biofilms; a new collaboration with Akara Robotics regarding UV-C disinfection of healthcare acquired pathogens; and a collaboration with academics at Umea University on disinfection and bleach resistance amongst the antibiotic-resistant pathogen Clostridioides difficile.

Throughout history most pathogens have been acquired by transmission from animal reservoirs (called a zoonotic infection). Coronavirus (COVID-19) and Ebola virus infection in humans (from bats and chimpanzees / gorillas respectively) and bovine tuberculosis infection in cattle (from badgers) are three examples of ongoing zoonotic diseases from wild animal populations. Our research focuses on the rapid development of CMV vaccine vectors for infectious disease in human and animal health, and as potential cancer therapeutics. A recent highlight was our work to develop a vaccine for Lassa fever - which is endemic in many West African countries. In collaboration with international partners we supported the development of a transmissable vaccine for use in the rats that spread Lassa fever, thus reducing its threat to humans.

Our patented vaccine technology is led by Professor Michael Jarvis and is being developed commercially via the UoP spin-out company The Vaccine Group.

As part of several collaborative projects, including one with partners in China, Dr Jarvis and Professor Mat Upton are developing vaccines to address antimicrobial resistance (AMR). Linked to this, Professor Upton has been part of the WHO Technical Advisory Group on Vaccines for AMR, helping to develop new guidelines on vaccine development.

Dr Feisal Subhan's research covers various aspects of respiratory physiology, including lung function in health and disease, breathlessness (dyspnoea) testing, exercise, smoking, markers of lung inflammation and heart rate variability. Recent work includes research on hypoxia and sniff nasal inspiratory pressure.