Project: Innate immune signalling
University of Cambridge
Tennis Court Road
The innate immune system has evolved to provide the first line of defence against invading pathogens. We want to understand how pathogens are detected by this system, how this detection informs the immune system to best respond to the infection and how we can use this information to design more effective vaccines. DNA is particularly powerful stimulator of the innate immune system and both foreign and self-DNA can initiate an immune response when found to be in the wrong place. We are interested in the mechanisms by which this DNA is sensed and how this sensing results in interferon and cytokine production. DNA vaccines make use of the innate immunostimulatory properties of nucleic acid to aid in the generation of powerful adaptive immune responses to the encoded antigen. We would like to understand how to optimise the innate immune response to generate the best possible vaccination against specific pathogens.
We are also interested in how pathogens have overcome these innate immune mechanisms by developing their own potent inhibitors of the host signalling mechanisms. For example vaccinia virus encodes at least ten proteins which can inhibit the NF-kB pathway at various points. By studying the interaction between the host response and the immune evasion mechanisms of pathogens we can both further the understanding of our own immune system and discover new ways to fight infectious diseases.
Christian Ku, Ben Trigg
- Ferguson BJ; Mansur DS; Peters NE; Ren H and Smith GL. DNA-PK is a DNA sensor for IRF-3-dependent innate immunity (2012). eLife Journal, in press.
- Ember SW; Ren H; Ferguson BJ; Smith GL. (12 Jul 2012). Vaccinia virus protein C4 inhibits NF-kB activation and promotes virus virulence. J Gen Virol
- Benfield CT; Mansur DS; McCoy LE; Ferguson BJ; Bahar MW; Oldring AP; Grimes JM; Stuart DI; (10 Jun 2011).Mapping the IKKbeta-binding interface of the B14 protein, a vaccinia virus inhibitor of IKKbeta-mediated activation of NF-kB. J Biol Chem. 286:20727-20735.
- Ferguson BJ; Li W; Khaled WT; Tevendale M; Stingl J; Poli V; Rich T; Salomoni P; et al (24 Mar 2009). PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool. Proc Natl Acad Sci U S A. 106:4725-4730.
- Ferguson BJ; Alexander C; Rossi SW; Liiv I; Rebane A; Worth CL; Wong J; Laan M; et al. (18 Jan 2008). AIRE's CARD revealed, a new structure for central tolerance provokes transcriptional plasticity. J Biol Chem. 283:1723-1731.