Insulin triggers glucose uptake into fat and muscle tissue, a process that is defective in type 2 diabetes. Insulin does this by triggering a complex cascade of actions once it binds to muscle and fat cells. We will analyse the function of a crucial protein within this cascade. This protein is mutated in humans with severe insulin resistance and our proposed project will dissect how this protein works potentially providing a novel drug target to treat diabetes.
A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.
Elucidating Crosstalk Between RhoGTPases And Polarity Proteins: The Interface Between Morphology, Immune Function And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
Major breakthroughs in cancer and autoimmunity require understanding the molecular basis of by which cell behaviour is controlled. We now know the key molecular players, but still need to determine how they interact within the cell to develop the best treatments and diagnostics. Recent breakthroughs now enable us to “watch” molecular interactions within the cell. We will use these approaches to determine how a key molecular switch is regulated in immune cells and cancer cells.
Parkinson’s disease (PD) is a complex neurological condition affecting 100,000 Australians. The primary clinical features of PD result from the selective loss of a specific type of neuron. It is currently unclear why these neurons are preferentially lost. We have identified a novel gene that causes early onset PD. This study will characterise the gene and determine the underlying disease mechanism. These studies will enable the development of novel therapies for treating PD.
Coupling The Cell Cortex To Membranes: Structural Basis For The Activation And Control Of Ezrin
Funder
National Health and Medical Research Council
Funding Amount
$587,548.00
Summary
Cells are dynamic: they change shape, communicate with each other and import/export signalling molecules. These dynamic processes are controlled via the interaction of the cell membrane with the underlying actin cytoskeleton and they are important for health, for example, they are critical for proper immune cell function. The goal of this project in to unravel the control of membrane dynamics by defining the interactions between the cell membrane and the proteins: ezrin and RhoA.
The co-ordinated regulation of cellular functions by hormones is vital to be able to respond to both immediate and long-term environmental changes and stresses. The stress hormone, adrenaline, affects in particular, the cardiovascular system, causing constriction of small arteries and increases in the force and rate of contraction of the heart, by binding to, and activating, adrenergic receptor proteins present on the cell surface. Activation of these receptors is implicated in the development o ....The co-ordinated regulation of cellular functions by hormones is vital to be able to respond to both immediate and long-term environmental changes and stresses. The stress hormone, adrenaline, affects in particular, the cardiovascular system, causing constriction of small arteries and increases in the force and rate of contraction of the heart, by binding to, and activating, adrenergic receptor proteins present on the cell surface. Activation of these receptors is implicated in the development of cardiac hypertrophy, as well as ventricular arrhthymias following ischaemia and reperfusion. Understanding the precise mechanisms or pathways of activation of these receptors is, therefore, of direct relevance to the treatment of these important clinical disorders. We have recently discovered a new protein, Gh, involved in the regulation of cellular functions by adrenergic receptors. The aims of this proposal are to determine the importance of Gh in the heart and understand the molecular mechanisms that control the function of this protein. Such insights are of paramount importance as they have direct applicability to our understanding of the heart s response to stress and may lead to new diagnostic or therapeutic approaches for the treatment of cardiac diseases.Read moreRead less
Investigation Of Cellular Abnormalities And Synapse Formation In DOCK8 Immunodeficiency
Funder
National Health and Medical Research Council
Funding Amount
$318,284.00
Summary
Why do some people get allergies? Or serious infections? To investigate this we will study mice and humans with a mutation in the DOCK8 gene. People with mutations in the DOCK8 gene get Hyper-IgE Syndrome and develop severe viral infections of the skin as well as allergic disease. By investigating how DOCK8 works in the cells of the immune system, we hope to understand why these infections and allergies occur and find out why these problems can also happen in those without this specific genetic ....Why do some people get allergies? Or serious infections? To investigate this we will study mice and humans with a mutation in the DOCK8 gene. People with mutations in the DOCK8 gene get Hyper-IgE Syndrome and develop severe viral infections of the skin as well as allergic disease. By investigating how DOCK8 works in the cells of the immune system, we hope to understand why these infections and allergies occur and find out why these problems can also happen in those without this specific genetic defect.Read moreRead less
Dissecting The Role Of Insulin-regulated Phosphorylation Of Rab Guanine Nucleotide Exchange Factors In GLUT4 Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
Diabetes and obesity are epidemic in the developed world. Impaired insulin action is a major cause. A key contributor is reduced glucose uptake into muscle and fat driving the pancreas to overproduce insulin. We have recently discovered three new molecules that we believe hold the secret to how insulin regulates the removal of the glucose from the blood stream after a meal. This proposal focuses on these three molecules and their regulation.