Queen's DTP: The role of inflammasome signalling in SARS-CoV-2 and RSV immunopathogenesis

SARS-CoV-2 is responsible for the current worldwide pandemic and huge mortality, particularly in the elderly. RSV causes devastating annual winter epidemics, particularly in young infants and the elderly. Therapeutic options for these viruses are either non-existent or suboptimal. Both viruses cause severe respiratory disease that is manifested by over-exuberant immune responses to infection. Both viruses primarily target the airway epithelium, which initiates inflammatory responses that likely cause the over-exuberant activation of innate immune cells, such as macrophages, associated with severe disease. However, the molecular mechanisms by which these respiratory viruses cause disease is poorly understood. We anticipate that inflammasome activation may be critical, as inflammasome activation causes both local and systemic inflammation. Therefore, this project will exploit novel models of SARS-CoV-2 and RSV infection based on well-differentiated primary human airway epithelial cell cultures and primary human macrophages to study the role of inflammasomes in virus-induced innate immune responses and the molecular crosstalk between the airway epithelium and innate immune cells that might elucidate disease mechanisms.  

This project will be ideal for an ambitious high-achieving student with a desire to help solve one of the greatest medical emergencies the world has known for over a century.