Regulation of interferon and innate signalling

ResearchCentre for Innate Immunity and Infectious Diseases > Regulation of interferon and innate signalling

macrophage and bacteriaRegulation of interferon and innate signalling

Research Group Head: Professor Paul Hertzog

The Regulation of interferon and innate signalling research group continues to focus on understanding the molecular regulation of immune responses to infection, inflammation, and cancer, which requires a systems approach. The interferon (IFN) family of cytokines, which are key regulators of immunity, is central to these processes. IFNs are produced in response to pathogen recognition by toll-like receptors (TLRs) and other receptors of ‘danger’ signals activated by infection or other cell death signals.

IFNs protect cells from viral infection, activate all effector cells of the immune response and can inhibit tumour cell growth. However, in certain situations, IFNs can be pro-inflammatory and have dose-limiting toxicity as therapies for viral infections and other clinical conditions, which can lead to autoimmune disease. Therefore, an understanding of IFN regulation, how and why IFNs are produced in different circumstances, how IFNs signal differently in different cells, and the discovery of mechanisms to regulate these effects selectively, are vital.

TLRs and IFNs use well-characterised signal transduction pathways such as NF-κB, IRF and STATs. However, there are other relatively uncharacterised transcription factor pathways such as the ETS factors, which scientists and students in the team are currently characterising. Furthermore, since cytokines do not act in isolation, scientists in the Regulation of interferon and innate signalling group are interested in the cytokine environment in which IFNs and other factors operate.

Research Projects:

 

Research Group:

Professor Paul Hertzog (Research Group Head)
Dr Nicky de Weerd
Dr Niamh Mangan, Fielding Foundation Fellow
Dr Amanda Rossiter, Sir Henry Wellcome Postdoctoral Fellow
Dr Michelle Tate, NHMRC Peter Doherty Fellow
Dr Nollaig Bourke
Dr Ross Chapman
Dr Helen Cumming

Selected publications:

de Weerd NA, Vivian JP, Nguyen TK, Mangan NE, Gould JA, Braniff SJ, Zaker-Tabrizi L, Fung KY, Forster SC, Beddoe T, Reid HH, Rossjohn J, Hertzog PJ. Structural basis of a unique interferon-β signaling axis mediated via the receptor IFNAR1. Nature Immunology. 2013 Sep;14(9):901-7.

Fung KY, Mangan NE, Cumming H, Horvat JC, Mayall JR, Stifter SA, De Weerd N, Roisman LC, Rossjohn J, Robertson SA, Schjenken JE, Parker B, Gargett CE, Nguyen HP, Carr DJ, Hansbro PM, Hertzog PJ. Interferon-ε protects the female reproductive tract from viral and bacterial infection. Science. 2013 Mar 1;339(6123):1088-92

Rusinova I, Forster S, Yu S, Kannan A, Masse M, Cumming H, Chapman R, Hertzog PJ. Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 2013 Jan;41(Database issue):D1040-6.

Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y, Loi S, Andrews D, Mikeska T, Mangan NE, Samarajiwa SA, de Weerd NA, Gould J, Argani P, Möller A, Smyth MJ, Anderson RL, Hertzog PJ*, Parker BS*. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nature Medicine. 2012 Aug;18(8):1224-31.

Mansell A, Smith R, Doyle SL, Gray P, Fenner JE, Crack PJ, Nicholson SE, Hilton DJ, O’Neill LA, Hertzog PJ. Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nature Immunology. 2006 Feb;7(2):148-55.