Research in our Division encompasses epidemiological and molecular studies on viruses and bacteria, as well as their interactions with the cell and host immune responses. This includes a genetic analysis of microbial populations and host-pathogen interactions during infection, the molecular basis of infection, and the immunology of vaccines.
Our studies allow us to investigate the genetic and functional mechanisms of host susceptibility to infection. By using zebrafish as a model of disease susceptibility, and patient groups with primary immunodeficiencies we are able to discover new causative mutations that allow us to probe the cellular pathways of infection. Unbiased proteomic and metabolomic approaches are also adopted to investigate how viral infection regulates critical aspects of immune cell metabolism. These methods, combined with informatics, statistical and mathematical modelling allow our researchers to probe the behavioural and environmental patterns leading to disease. This systems-level method of thinking maximises our understanding of how infectious diseases are transmitted and guides the development of diagnoses in clinical practice. It also helps us formulate strategies for public health, infection control, antimicrobial resistance, and pathogen biology, resulting in more effective interventions, both in the UK and abroad.
In addition to these broader scientific approaches, we also use classical molecular and structural biological approaches to probe host-pathogen interactions. For example, using these methods we are gaining an understanding of how RNA viruses (e.g. Ebola, influenza, common cold, measles, West Nile virus) assemble and recognise host cells, how they deliver their genetic material into the host, and how innate immune responses are generated, amplified and regulated. Our work on retroviruses (a type of RNA virus) has allowed us to find novel strategies to target latent HIV-1, as well as enabling the development of novel vectors for therapeutic gene delivery.
Other viruses, such as human cytomegalovirus (HCMV), may never cause symptoms following infection, and remain latent for the rest of the person's life. Indeed, HCMV is found throughout the globe and in all socioeconomic groups; it infects 60% - 70% of adults in industrialized countries and almost 100% in emerging countries. However, these infections can become life-threatening for individuals whose immune systems are compromised or immature (such as HIV-infected persons, organ transplant recipients, newborn infants). Another of our aims is to discover how they are able to persist in healthy individuals by evading the immune response, and what cellular factors control this viral latency and their eventual reactivation. Ultimately, answers to these questions will provide us with a clear strategy for treating latent infections.