NHMRC Research Fellowship (PRF): Protein trafficking in inflammation and disease (2011–2016)
Intracellular trafficking pathways impact on all cell functions and all human diseases. My research in cell biology has had a major impact on our understanding of protein trafficking and secretion. Discoveries from my lab have revealed new trafficking pathways in cells. In epithelial cells we defined pathways governing cell polarity and cell adhesion. In macrophages we characterized recycling endosomes and key molecules for trafficking and secretion of inflammatory cytokines during immune responses. These studies have generated fundamental insights into the cellular control of inflammation, providing new avenues for blocking the damaging secretion of cytokines in chronic inflammatory disease through gene silencing and drug development. The proposed research program builds on our expertise in cell biology to pursue the following specific projects -
i) New targets for in vivo control of TNF secretion in inflammatory disease are being developed through an industry collaboration, ii) Recycling endosome Rabs and SNAREs (including disease genes) are being characterized in the sorting and secretion of cytokines, in phagocytosis and cell polarity and, iii) Trafficking pathways and molecules required for bacterial invasion of host cells are being studied under the auspices of a new collaborative program.
These projects are underpinned by cutting-edge resources and expertise in live cell fluorescence imaging, high throughput RNAi, ultrastructural microscopy and in vivo mouse models, developed at IMB by my group and collaborators. Research outcomes will impact on inflammatory diseases, inherited immuno-deficiencies and cancer by generating new knowledge and innovative therapeutic strategies. This research contributes nationally through collaborations, technology development and advancement of science, it addresses key national research priorities in chronic and infectious diseases and in biosecurity, and it will continue to draw international investment and recognition.