Research
The lab’s research projects are focused around understanding how our cells sense and respond to virus infection and how this impacts innate and adaptive immunity:
1) The innate immune response to DNA.
Pattern recognition receptors (PRRs) directly recognise pathogen- or danger-associated molecular patterns. Nucleic acids are a powerful immunostimulatory agents that triggers PRRs to warm of infection or tissue damage. Our innate immune system has evolved multiple mechanisms to respond to the presence of abnormally structured or mis-localised DNA and RNA. We are exploring the molecular mechanisms of innate immune nucleic acid sensing and is physiological consequences across multiple species.
Nucleic acid sensing by intracellular PRRs has a particular importance in triggering the initial type I and type III interferon responses in response to virus infections. Our lab is interested to understand how different nucleic acid sensing PRRs impact on host defence against a range of DNA and RNA viruses.
2) Cell death in innate immunity
The role of cell death in anti-viral defence is well establised, although 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 how they regulate nucleic acid sensing mechanisms.
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 are developing systems to analyse how and where the initial triggers of long lasting memory occur.
Post-doctoral research associates:
Dr Marisa Oliveira
PhD students:
Ms Helena Teague
Ms Dayana Hristova
Ms Emma Wagner
Mr Rahul Singh
Ms April D'Arcy
Publications
- Oliveira M, Rodrigues DR, Guillory V, Kut E, Giotis ES, Skinner MA, Guabiraba R, Bryant CE, Ferguson BJ Chicken cGAS senses fowlpox virus infection and regulates macrophage effector functions (2021) Frontiers in Immunology, 01 Jan 2020, 11:613079
- JB Aggio, V Krmeská, BJ Ferguson, PF Wowk, AG Rothfuchs, Vaccinia Virus Infection Inhibits Skin Dendritic Cell Migration to Draining Lymph Nodes (2021) The Journal of Immunology 206 (4), 776-784
- ER Eden, L Wong, A Martello, BJ Ferguson, J Edgar. Exploiting connections for viral replication (2021) Frontiers in Cell and Developmental Biology 9, 284
- DB Hristova, KB Lauer, BJ Ferguson, Viral interactions with non-homologous end-joining: a game of hide-and-seek (2020) Journal of General Virology, jgv001478
- EV Shmeleva, GL Smith, BJ Ferguson, Enhanced efficacy of vaccination with vaccinia virus in old versus young mice (2019) Frontiers in Immunology, https://doi.org/10.3389/fimmu.2019.01780
- PF dos Santos, J Van Weyenbergh, M Delgobo, DO Patricio, BJ Ferguson, R Guabiraba, T Dierckx, SM Menezes, A Bafica, DS Mansur ISG15-Induced IL-10 Is a Novel Anti-Inflammatory Myeloid Axis Disrupted during Active Tuberculosis (2018) Journal of Immunology, ji1701120
- BJ Trigg, KB Lauer, PF dos Santos, H Coleman, G Balmus, DS Mansur and BJ Ferguson (2017) The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection (2017) Viruses 9(11), 342; doi:10.3390/v9110342
- 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 (2016) Genome-wide analyses reveal a highly conserved Dengue virus envelope peptide which is critical for virus viability and antigenic in humans Sci Rep. 2016; 6: 36339.
- 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* (2016) LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation J Exp Med 213 (12), 2671-2689 *co-corresponding authorship
- RP Sumner, H Ren, BJ Ferguson and GL Smith (2016) Increased attenuation but decreased immunogenicity by deletion of multiple vaccinia virus immunomodulators, Vaccine 34 (40), 4827-4834
- BJ Ferguson, S Newland et al. (2015) The Schistosoma mansoni T2 ribonuclease omega-1 modulates inflammasome-dependent IL-1β secretion in macrophages Int J Parasitology 45( 13),809–813
- BJ Trigg and BJ Ferguson (2015) Functions of DNA damage machinery in the innate immune response to DNA virus infection Current Opinion in Virology 15, 56-62
- H Ren, BJ Ferguson, C Maluquer de Motes, RP Sumner, L Harman, GL Smith (2015) Enhancement of CD8+ T‐cell memory by removal of a vaccinia virus NF‐κB inhibitor. Immunology 145 (1), 34-49
- NE Peters, BJ Ferguson, M Mazzon, AS Fahy, E Krystofinska, R Arribas-Bosacoma, LH Pearl, H Ren, GL Smith (2013) A mechanism for the inhibition of DNA-PK mediated DNA sensing by a virus PloS Pathogens 9(10): e1003649
- GL Smith, CTO Benfield, CM de Motes, M Mazzon, SWJ Ember, BJ Ferguson, RP Sumner (2013) Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity Journal of General Virology, Nov;94(Pt 11):2367-92
- M Mazzon, NE Peters, C Loenarz, EM Krysztofinska, SWJ Ember, BJ Ferguson, GL Smith (2013) A mechanism for induction of a hypoxic response by vaccinia virus Proc Natl Acad Sci USA, 110 (30), 12444-12449
- BJ Ferguson, CTO Benfield, H Ren, VH Lee, GL Frazer, P Strnadova, RP Sumner, GL Smith (2013) Vaccinia virus protein N2 is a nuclear IRF3 inhibitor that promotes virulence J Gen Vir, 94 (9), 2070-2081
- BJ Ferguson; Mansur DS; Peters NE; Smith GL. (2012) DNA-PK is a DNA sensor for IRF-3-dependent innate immunity eLife 2012;1:e00047
- Mansur DS; Maluquer de Motes C; Unterholzner L; Sumner RP; BJ Ferguson; Ren H; Strnadova P; Bowie AG; Smith GL. (2012) Poxvirus targeting of E3 ligase beta-TrCP by molecular mimicry: A mechanism to inhibit NF-κB activation and promote immune evasion and virulence. PLoS Pathog. Feb;9(2):e1003183
- Li W*; BJ Ferguson*; Khaled WT; Tevendale M; Stingl J; Poli V; Rich T; Salomoni P; Watson CJ. (2009). PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool. Proc Natl Acad Sci USA. 106(12):4725-30. *Joint authorship
- BJ Ferguson; Alexander C; Rossi SW; Liiv I; et al. (2008) Aire’s CARD revealed; a new structure for central tolerance provokes transcriptional plasticity. J Biol Chem. 283:1723-1731
- BJ Ferguson; Dovey CL; Lilley K; Wyllie AH; Rich T. (2007) Nuclear phospholipase C gamma: punctate distribution and association with the Promyelocytic leukaemia protein. J Prot Research, 6(5):2027-32.
- Varadaraj A; Dovey CL; Laredj L; BJ Ferguson; Alexander CE; Wyllie AH; Rich T. (2007) Evidence for the receipt of DNA damage stimuli by PML nuclear domains. J Pathology. 211(4):471-80.
- BJ Ferguson; Esposito D; Jovanovic J; Sankar A; Driscoll PC; Mehmet H. (2007) Biophysical and cell-based evidence for differential interactions between the death domains of CD95/Fas and FADD. Cell Death and Differentiation. 14(9):1717-9.
