Dr Brian Ferguson

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

1) The innate immune response to DNA.

DNA is a powerful immunostimulatory agent and our innate immune system has evolved multiple mechanisms to respond to the presence of DNA outside of its normal localisation (inside nuclei and mitochondria). We recently discovered that DNA-PK can activate the IRF-3 dependent production of interferons and cytokines in response to cytoplasmic DNA. We have a Wellcome Trust funded project to extend this analysis to other components of the non-homologous end-joining machinery, and their impact on DNA virus infection. 

2) Cell death in innate immunity

The role of cell death in anti-viral defence is well establised. However its function in activating anti-viral immunity is less clear. By analysing signalling pathways that control the switch between pro-inflammatory gene activation and cell death we can probe the consequences of viral-induced cell death in anti-viral defence. We are specifically interested in the role of linear ubiqiutin chains in regulating these processes and in collaboration with Professor Henning Walczak at UCL we are understanding how ubiqutin chains function in pattern recognition receptor signalling and anti-viral defence. 

3) 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 in collaboration with Professor Geoffrey Smith and Professor David Tscharke to understand the mechanistic basis of how these mutant viruses modulate immunological memory gives us the potential to rationally design improved vaccines.

Collaborations:

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

Professor Geoffrey Smith, University of Cambridge, UK

Professor David Tscharke, Australian National Univserity, Canberra, Australia

Professor Henning Walczak, University College London, UK

Professor Steve Jackson, Gurdon Institute, Cambridge, UK

Dr Antonio Rothfuchs, Karolinska Institute, Stockholm, Sweden

Dr Valentyn Oksenych, Norwegian University of Science and Technology,Trondheim, Norway