The role of actin in driving bulk endocytosis in neurons and neurosecretory cells. Synaptic release of neurotransmitter is essential for neuronal communication. Following fusion, synaptic vesicle membrane is incorporated into the plasma membrane and retrieved by endocytosis to recover both lipids and essential vesicular proteins. The project will characterise how the actin cytoskeleton perform this function.
The combined use of proteomics and small molecules for target identification and pathway analysis. This project intends to investigate how a series of new small molecules identified from our research to improve the metabolic effects of insulin. This project will integrate medicinal chemistry with proteomics and metabolic biology to identify the cellular targets and their mechanism of action.
Muscling in on the brain. This project investigates an enzyme that 'matures' neurotransmitters in the brain that regulate food intake, energy expenditure and blood pressure by the brain; these neurotransmitters arise from the same precursor molecule. This project will show the physiological relevance of this enzyme in obesity.
Rapid mapping of genes for complex traits. This project will develop a new resource that will allow rapid identification of genes controlling complex traits. This world-leading resource will improve knowledge of diseases like diabetes and neurological diseases.
Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in li ....Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.Read moreRead less
Explaining the differences in affinity and of carbohydrate binding of the glycogen-sensing enzyme, AMP-protein activated kinase (AMPK). This project will provide fundamental molecular knowledge of how a complex enzyme, AMPK is controlled by the major sugar molecule, glycogen. Our research will increase our understanding of its role in metabolic diseases such as Type 2 diabetes and obesity.
Structural understanding of the degradation of glucose polymers. Understanding starch and glycogen breakdown at the molecular level is important for human nutrition and health. The understanding from this project will lead to new means for the control and mitigation of nutritional diseases, such as diabetes and obesity, as well as improved foods.
Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as h ....Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as heat exposure and exercise. The non-invasive tool aims to enable us to assess adaptations in microvasculature health, improving our understanding of cardiovascular diseases and type 2 diabetes and potentially reducing the impact of costly and debilitating morbidities such as nephropathy, neuropathy, retinopathy, impotence and skin ulceration.Read moreRead less
Investigating the functional interaction between vasopressin and angiotensin receptors. Kidney disease resulting from diabetes is a major health issue for Australians, and indigenous Australians in particular. This project aims to enable improved therapies to be developed, as well as better inform doctors regarding the use of potential combinations of existing pharmaceuticals to treat this condition.