Phosphatase Regulators Mediate Long-term Changes In Presynaptic Terminals
Funder
National Health and Medical Research Council
Funding Amount
$984,163.00
Summary
The strength of communication between each nerve cell in the brain depends on how active that nerve cell has been. This enables the brain to be adaptable and is a way for the brain to set up circuits that underlie how we learn and remember. More or less release of chemical messengers (neurotransmitters) into nerve cell junctions changes the strength of nerve cell communication. We have discovered a new chemical signalling pathway controlling neurotransmitter release.
The Role Of Parasite Adhesins In Plasmodium Falciparum Invasion Of Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$385,434.00
Summary
Invasion of red blood cells is essential for the survival of malaria parasite within the human host. Red blood cell invasion is mediated by recognition of parasite proteins to specific blood surface receptors. My research focuses on understanding these parasite protein-host receptor interactions with emphasis on translating these findings as novel approaches for the prevention and treatment of malaria.
Metabolic Wiring In Adipocytes - Unique Role In Maintaining Long-term Health
Funder
National Health and Medical Research Council
Funding Amount
$1,077,886.00
Summary
Fat cell metabolism is wired to optimize the cell’s ability to make and store lipid while programming the cell to fulfil its function in whole body metabolism. We will: 1) map fat cell metabolism under optimal and insulin resistant conditions; 2) explore the role of 3 nodes in his metabolic circuit predicted as control points; 3) use a novel genetically engineered mouse model to explore the functional significance of fat cell metabolism in whole body insulin sensitivity.
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.
Molecular Mechanisms Of Dynamin-mediated Endocytosis In Nerve Terminals
Funder
National Health and Medical Research Council
Funding Amount
$1,033,626.00
Summary
Neurons communicate by neurotransmitter release from synaptic vesicles stored in nerve endings. There is a finite vesicle number, so they are recycled (endocytosis) by the protein dynamin. Our aim is to reveal how new vesicles are produced when the brain is under very high activity, to better understand diseases of the synapse like epilepsy. We propose that two forms of the dynamin gene mediate this process, only under conditions of high neuronal firing, such as occurs during a seizure.
Skeletal Muscle Signal Transduction Related To Exercise, Metabolic Disease And Human Health
Funder
National Health and Medical Research Council
Funding Amount
$557,298.00
Summary
Exercise is one of the best prevention and treatment strategies for all major human diseases. Despite these well documented advantages, we still do not know exactly how exercise produces these benefits at the molecular level. A comprehensive understanding of this will lead to new avenues to treat many diseases. This project will monitor thousands of molecular changes that occur in human muscle biopsies following exercise and create the world’s first molecular blueprint of exercise.
Human Tyrosine Hydroxylase Isoforms And Susceptibility Of Dopaminergic Neurons To Degeneration In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$359,683.00
Summary
In Parkinson's disease there is major loss of the dopaminergic neurons of the substantia nigra. We are investigating how the control of dopamine synthesis may affect the differential loss of dopaminergic neurons in Parkinson's disease. Understanding why certain dopaminergic die in Parkinson's disease and others do not will help the development of new treatment strategies for Parkinson's disease.
Phosphorylation Of Synaptic Vesicle Glycoprotein 2 (SV2) Regulates Endocytosis Of Synaptotagmin For Synaptic Transmission
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Antiepileptic drugs typically target ion transporters or neurotransmitter receptors. Synaptic vesicle glycoprotein 2 (SV2) is a rare example of a synaptic vesicle recycling protein that is the target of an antiepileptic drug. It also binds botulinum and tetanus neurotoxins. We discovered SV2 contains activity-dependent signalling molecules. Charactersation of these molecules and will allow a deeper understanding of the molecular basis for its role in epilepsy and toxin action.
Dissecting Rapamycin Sensitive And Insensitive Effects Of MTOR
Funder
National Health and Medical Research Council
Funding Amount
$1,183,241.00
Summary
All cells possess machinery that can sense nutrient availability and trigger cell growth and nutrient storage pathways. However, nutrient oversupply is detrimental to health. Recently, it was shown that drugs that inhibit the nutrient sensors have life extending effects. Our laboratory has discovered a novel mechanism by which these drugs might be mediating these beneficial effects that could change the way we think about the beneficial effects of these drugs and their mode of action
Role Of Oxidative Stress In Activating ATM To Protect Against Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
ATM is the protein defective in the human genetic disorder ataxia-telangiectasia (A-T). This project is designed to investigate how this protein is activated by oxidative stress. The study is largely a mechanistic one, to investigate changes occurring in ATM as part of the activation process. There is evidence that ATM exists in the cytoplasm in neuronal cells and understanding its function in these cells may assist in understanding the basis for neurodegeneration in A-T.