Macrophage Biology in Development, Health and Disease
Macrophages are the classic two-edged sword. They are essential for development and homeostasis, innate and acquired immunity and tissue repair, but also drive the pathology of inflammatory, infectious, malignant and traumatic disease processes. Macrophages are the target of countless therapeutic agents that modulate their recruitment and activation or secreted pro-inflammatory products. In simple terms, there are circumstances where more or less macrophage activity may be therapeutically desirable even within the course of one disease process. The macrophage colony-stimulating factor receptor (CSF1R) is a ligand-dependent receptor tyrosine kinase that controls macrophage survival, proliferation, differentiation and gene expression. The CSF1R gene became more clearly relevant to human disease biology with the identification of dominant coding mutations associated with neurodegenerative disease and recessive mutations impacting skeletal and brain development. Our research group has invested in novel reagents and animal models to dissect the function of CSF1R-dependent macrophage populations. Our vision is to translate that investment into understanding macrophage ontogeny, differentiation and homeostasis and a rational basis for the use of CSF1R agonists and antagonists as therapies.
PhD Student Vacancies
We are currently recruiting PhD students for two NHMRC-funded projects.
Successful applicants will demonstrate academic achievement in one or more of molecular and cellular biology, physiology and immunology
The projects will involve significant work with preclinical animal models and so prospective student should be willing to undertake this type of research, and previously experience would be well regarded.
Macrophage-driven lipid metabolism in health and disease
Metabolic diseases, including obesity and its associated spectrum of pathologies, represent some the greatest health challenges we currently face. Macrophages, cells of the innate immune system, regulate many aspects of metabolism in health and disease. They form abundant resident populations in major metabolic tissues such as liver and fat, where they regulate energy homeostasis and prevent inflammation. But recruited or activated macrophages contribute to inflammation-driven metabolic maladaptation that is central to the development of metabolic diseases, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease. We have discovered that stimulating macrophages can induce liver growth and alter body composition – promoting increased lean mass, reduced fat mass and reduced liver fat. We hypothesise that macrophages are a component of the regulatory network that controls metabolic homeostasis, which has clear therapeutic implications for obesity and related pathologies. This PhD project will investigate the mechanisms underlying macrophage regulation of metabolism in health and disease
Regulation of resident tissue macrophage development and function
Macrophages are cells of the innate immune system that also contribute to development and homeostasis. They are an abundant cell population in every tissue in the body including the brain. The differentiation of macrophages is controlled by two growth factors, macrophage colony-stimulating factor (CSF1) and interleukin 34 (IL34) which each signal through a shared receptor (CSF1R) expressed only by cells of the macrophage lineage. This project seeks to understand how the expression of CSF1R and its two ligands is controlled through the generation and analysis of transgenic mouse models and to use that knowledge to dissect the ways in which tissue macrophages develop and are maintained throughout life.