Protein trafficking and inflammation

Our projects make use of approaches including:

• Tagging, mutation and expression of genes and proteins for advanced live cell imaging, microscopy and 3D image analysis and visualization.
• Mapping protein-protein interactions and signalling networks with proteomic and biochemical approaches.
• Exploring drug effects and gene knockouts and gene expression in cells, organoids and animal models of disease.

Project 1. Macropinocytosis and phagocytosis are pathways for pathogen entry and cell activation in macrophages. We are defining roles for individual Rab GTPases as regulators of membrane changes, receptor signaling and recycling, endocytic uptake and degradation. Advanced imaging and modelling are also used to examine macropinosome and phagosome formation. This project aims to find molecules and membranes that can be targeted to fight infection and inflammation.

Project 2. Toll-like receptors (TLRs) respond to pathogens and tissue damage and activate macrophages to initiate immune and inflammatory responses. We study signalling and cytokine secretion. We have discovered roles for lipid kinases, GTPases, signaling adaptors and trafficking proteins in these pathways that can potentially be targeted for infection, autoimmune disease, Alzheimer’s, lung inflammation and other chronic diseases.

Project 3. Macropinocytosis in cancer cells. Mutations in some cancer cells increase macropinocytosis for nutrient uptake which allows aggressive cancers to survive and spread. We are identifying macropinosome regulators in cancer cells that could be new drug targets in cancer.  We are examining the roles of macropinocytosis in cancer cell survival and metastasis in cell cultures, organoids and tumour models.

Project 4. Cilia and kidney disease. Epithelial cells and other cells have cilia, or cell antennae, to control tissue development, function and disease. Genetic mutations affecting cilia in, leading to a wide range of symptoms in inherited ciliopathies.  We study Rab GTPases and other regulators to gain insights into cilia function and dysfunction in disease.

Traineeships, honours and PhD projects are offered in these areas.