Centre for Innate Immunity & Infectious Disease

Molecular regulation of immunity

Laboratory Head: Professor Paul Hertzog

Molecular regulation of immunity laboratory

Understanding the molecular regulation of immune responses to infection, inflammation and cancer requires a systems approach. The interferon (IFN) family of cytokines, key regulators of immunity, is central to these processes. IFNs are a multi-gene family whose roles and modus operandi remain unclear. They 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 therapeutically have dose-limiting toxicity which, in the extreme, can lead to autoimmune disease. Therefore an understanding of the regulation of which 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-characterized signal transduction pathways such as NFkB, IRF and STATs. However, there are other relatively uncharacterized transcription factor pathways such as the ETS factors, which scientists and students in the MIR team are currently characterizing. Furthermore, since cytokines do not act in isolation, scientists in this team are interested in the cytokine environment in which IFNs and other factors operate.

The team encourages a multidisciplinary approach to all research projects. Areas of investigation include:

• Structure-function characteristics of ligand-receptor interactions
• Signaling protein interactions and modifications
• Transcriptional regulation of gene expression (gene expression microarrays, transcription factor binding, miRNA)
• Bioinformatics integration of signaling components and pathways
• Generation and use of gene targeted mice (knockouts, knockins, transgenics and reporters) in studies of signal transduction in vivo and in models of human disease including lung infection and inflammation, septic shock, systemic viral infection and cancers including breast and mesothelioma