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, Doctor Philip Warburton).

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.

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: 

• Protection from hepatitis C virus infection (Professor Matthew Cramp)
• Lipid metabolism and the pathogenesis and treatment of non-alcoholic steatohepatitis (Doctor David Sheridan)
• Alcoholic hepatitis (Doctor Ashwin Dhanda)
• Molecular virology of hepatitis C and other hepatitis viruses (Doctor Daniel Felmlee).

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.

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).

(Doctor Andrew Foey, Doctor Gyorgy Feyer)

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

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.

Our patented vaccine technology is being developed commercially via the UoP spin-out company The Vaccine Group.

The skeleton constantly remodels in response to changes in mechanical load, serum calcium and micro-damage. At a cellular level remodelling is performed by osteoblasts that secrete and mineralise new bone matrix and osteoclasts that resorb bone. Osteoblast and osteoclast activity is tightly regulated such that during each remodelling cycle osteoblast formation is temporally coupled to resorption ensuring there is little net bone loss. However, this balance is disrupted in many skeletal disorders such as post-menopausal osteoporosis, breast and prostate cancer. 

Our work aims to understand the mechanisms leading to the disruption of bone cell activity and assess the beneficial impact of potential novel nutritional factors on tumour and bone cell function.