Host-pathogens interactions

Mission: To understand the molecular biology of viruses and bacteria that cause disease in humans, animals and plants, and to translate these findings into new tools for prevention, detection and eradication of these pathogens.

Viruses and bacteria are the cause of significant disease in humans, animals and plants. For example, bacteria are developing resistance to current antibiotics, threatening our ability to treat common infectious diseases, resulting in prolonged illness, disability, and death. Viral infections are also a cause of global mortality and morbidity, with pandemic virus being the most significant human disease risk in the UK, according to the National Risk Register of Civil Emergencies (e.g. COVID-19). To reduce the risks of these and other infections, our research uses molecular and cellular techniques, combined with structural and chemical approaches, to understand in molecular detail how these pathogens grow, cause disease and evade treatment. We harness our knowledge of these fundamental processes to devise new approaches to prevent and treat infectious disease.

Key areas of focus:

• Understanding virus lifecycles from infection to release using high-resolution structural and imaging approaches.
• Leveraging expertise in chemical biology to interrogate infection and develop novel strategies for anti-infectives.

Key discoveries made:

• The single-stranded RNA genomes of many viral pathogens are a “self-instruction manual” for the production of the infectious virions
• Bunyaviruses require cellular potassium to infect cells, a finding that we are harnessing to repurpose clinically-approved drugs to treat these viral infections
• Activation of an IL-6 signalling axis drives autocrine STAT3 activation, providing an opportunity to use clinically approved drugs to treat HPV-mediated cervical cancer
• Oncogenic herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) sequesters a host cell complex, hTREX, to enhance viral mRNA processing and replication, a finding that has allowed us to inhibit KSHV replication
• Computational drug design has yielded β-lactamase inhibitors which circumvent evolved resistance to many current antibiotics