Research Activities

=Overall interest is in the molecular regulation of signal transduction in innate immunity. In particular our group is interested in pattern recognition receptor signaling, the elicited transcriptional responses including IRF, STAT, ETS and NFκB pathways and the ensuing cytokine responses. The particular cytokines of interest are the type I interferons (IFNs). We investigate the mechanisms of signaling beginning at engagement of the receptors, IFNAR1 and IFNAR2. Receptor function is studies using human cell systems, genetically modified mouse models, protein-protein interactions, structural biology, imaging and signal transduction studies. We have discovered a new family member involved in mucosal immunity called IFN epsilon which has special functions in the female reproductive tractinfections, inflammatory conditions and cancer. We also investigate negative regulation, of signalling by the SOCS family of cytokines and micro-RNA and other epigenetic mechanisms. We are investigating their regulation of IFN (α, β and γ) as well as TLR signaling. One outcome of our research is a growing capability in cell based screens for activators and inhibitors of innate immunity signaling. We are investigating the global nature of TLR/cytokine/interferon signaling using transcriptomics incorporated with bioinformatics to predict regulatory networks, disease signatures and identify novel transcriptional regulation candidates. One outcome is the INTERFEROME.org database for annotating response pathways. We have a longstanding expertise in the generation of genetically modified mice and their pathophysiological characterisation. Disease models include viral and bacterial infections and models of tumourigenesis. .

Research Keywords

Researching in the following areas: Interferons, Animal models - Mice, Inflammatory disease, Innate immunity, Functional genomics