The lab’s research projects are focused around the innate immune responses to virus infection in three main areas:

1) The innate immune response to viral nucleic acids.

Nucleic acids are powerful immunostimulatory agents. Sensing of damaged or mis-localised nucleic acids by pattern recognition receptors underlies multiple pathologies and is especially important in the context of anti-viral immunity. During DNA virus infection, the ability of our cells to sense viral genomic DNA it critical for mounting an interferon response. We discovered that DNA-PK can activate the IRF-3 dependent production of interferons and cytokines in response to viral DNA and are researching the intriguing links between the innate immune system and DNA damage response signalling pathways. We have Wellcome Trust and BBSRC funded projects to study these systems across multiple species.

2) Vaccinology

There are many fundamental questions about the development of immunological memory which remain poorly understood. It is clear that the initial detection of a vaccine vector by the innate immune system has long lasting consequences for the development of memory responses. We have developed a panel of mutant viruses which have differential impacts on the development of lymphocyte memory. We have an MRC funded project to understand the mechanistic basis of how these mutant viruses modulate immunological memory gives us the potential to rationally design improved vaccines.

3) Linear ubiquitin chains in anti-viral immunity

Linear (or Met1) ubiquitin chains regulate multiple immune signalling pathways, especially those leading to NF-Kb activation. We are interested in how this post-translational modification regulates the signalling outputs downstream of pattern recognition receptors during virus infection.

Collaborators:

Professor Daniel Mansur, University of Santa Catarina, Florianopolis, Brazil

Professor Geoffrey Smith, University of Cambridge, UK

Professor David Tscharke, Australian National University, Canberra, Australia

Professor Henning Walczak, University College London, UK

Professor Steve Jackson, Gurdon Institute, Cambridge, UK

Dr Antonio Rothfuchs, Karolinska Institute, Stockholm, Sweden

Dr Tim Halim, Cancer Research Institute, Cambridge, UK

Professor Alan Melcher, Institute of Cancer Research, London, UK

Professor Kevin Harrington, Institute of Cancer Research, London, UK

Dr Rodrigo Guabiraba, INRA, Tours, France

Professor Clare BryantUniversity of Cambridge, UK

Dr Yorgo ModisUniversity of Cambridge, UK