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Dr Brian Ferguson

University Lecturer

Project: Innate immune signalling, anti-viral immunity, vaccinology

Department of Pathology
University of Cambridge
Tennis Court Road
Cambridge
CB2 1QP

Office Phone: +44 (0)1223 333730

Research themes

Immunology:

Research Interests

Ferguson Research

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.

Post-doctoral research associates:

Kathi Lauer, Zhenya Shmeleva

Graduate Students:

Ben Trigg, Delphine Depierreux

Research Assistant:

Ana Moldoveanu

Key Publications

Genome-wide analyses reveal a highly conserved Dengue virus envelope peptide which is critical for virus viability and antigenic in humans
RC Fleith, FP Lobo, PF dos Santos, MM Rocha, J Bordignon, DM Strottmann, DO Patricio, WR Pavanelli, M Lo Sarzi, CN Dos Santos, BJ Ferguson, DS Mansur
Scientific Reports 6, Article number: 36339
2016
LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation
J Zinngrebe, E Rieser, L Taraborrelli, N Peltzer, T Hartwig, H Ren, I Kovács, C Endres, P Draber, M Darding, S von Karstedt, J Lemke, B Dome, M Bergmann , BJ Ferguson*, H Walczak*
J Experimental Medicine (In Press)
2016
Increased attenuation but decreased immunogenicity by deletion of multiple vaccinia virus immunomodulators
RP Sumner, H Ren, BJ Ferguson, GL Smith
Vaccine Volume 34, Pages 4827–4834
2016
The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1beta secretion in macrophages
BJ Ferguson, S Newland, SE Gibbs, P Tourlomousis, P Fernandes dos Santos, MN Patel, SW Hall, H Walczak, G Schramm, H Haas, DW Dunne, A Cooke, and P Zaccone
International Journal for Parasitology Volume 45, Issue 13 Pages 809–813
2015
Functions of DNA damage machinery in the innate immune response to DNA virus infection
BJ Trigg and BJ Ferguson
Current Opinion in Virology Volume 15, Pages 56–62
2015
International Union of Basic and Clinical Pharmacology. XCVI. Pattern Recognition Receptors in Health and Disease
CE Bryant, S Orr, BJ Ferguson, MF Symmons, JP Boyle, and TP Monie
Pharmacological Reviews vol. 67 no. 2 462-504
2015
Enhancement of CD8+ T‐cell memory by removal of a vaccinia virus NF‐κB inhibitor
H Ren, BJ Ferguson, C Maluquer de Motes, RP Sumner, L Harman, GL Smith
Immunology 145 (1), 34-49
2015
A mechanism for the inhibition of DNA-PK mediated DNA sensing by a virus
NE Peters, BJ Ferguson, M Mazzon, AS Fahy, E Krystofinska, R Arribas-Bosacoma, LH Pearl, H Ren, GL Smith 
PloS Pathogens 9(10): e1003649
2013
Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity
GL Smith, CTO Benfield, CM de Motes, M Mazzon, SWJ Ember, BJ Ferguson, RP Sumner
Journal of General Virology, 94: 2367-2392
2013
A mechanism for induction of a hypoxic response by vaccinia virus
M Mazzon, NE Peters, C Loenarz, EM Krysztofinska, SWJ Ember, BJ Ferguson, GL Smith
Proceedings of the National Academy of Sciences, 110 (30), 12444-12449
2013
Vaccinia virus protein N2 is a nuclear IRF3 inhibitor that promotes virulence 
BJ Ferguson, CTO Benfield, H Ren, VH Lee, GL Frazer, P Strnadova, RP Sumner, GL Smith
Journal of General Virology, 94 (9), 2070-2081
2013
Poxvirus Targeting of E3 Ligase β-TrCP by Molecular Mimicry: A Mechanism to Inhibit NF-κB Activation and Promote Immune Evasion and Virulence
DS Mansur, CM de Motes, L Unterholzner, RP Sumner, BJ Ferguson, H Ren, P Strnadova, AG Bowie, GL Smith
PLoS pathogens 9 (2), e1003183
2013
Vaccinia virus protein C4 inhibits NF-κB activation and promotes virus virulence
SWJ Ember, H Ren, BJ Ferguson, GL Smith
Journal of General Virology 93 (Pt 10), 2098-2108
2012
DNA-PK is a DNA sensor for IRF-3-dependent innate immunity
BJ Ferguson, DS Mansur, NE Peters, H Ren, GL Smith
eLife Sciences 1 e00047
2012