Protein Partners Of Rapsyn That Regulate Acetylcholine Receptor Clustering
Funder
National Health and Medical Research Council
Funding Amount
$411,000.00
Summary
Spinal nerves control our limb muscles by releasing chemical signals directly onto the surface of muscle fibres that they contact. These chemical signalling contacts are called synapses. They are like the synapses between nerve cells in our brains but easier to study, meaning that we can make more rapid progress in understanding how synapses work. The sensor receptors for chemical signals at the nerve-to-muscle synapse are held in place on the muscle fibre surface by a protein called rapsyn. In ....Spinal nerves control our limb muscles by releasing chemical signals directly onto the surface of muscle fibres that they contact. These chemical signalling contacts are called synapses. They are like the synapses between nerve cells in our brains but easier to study, meaning that we can make more rapid progress in understanding how synapses work. The sensor receptors for chemical signals at the nerve-to-muscle synapse are held in place on the muscle fibre surface by a protein called rapsyn. In turn, rapsyn must be organized by other chemical signals from the nerve, but we don't know exactly how this happens. When the receptors become disorganized at the synapse, in diseases such as Myasthenia Gravis, we lose control of our muscles. This project will employ newly developing techniques of proteomics and genomics to identify new proteins that bind to rapsyn and to test how they work to organize receptors at the synapse. By identifying the proteins that control rapsyn we may be able to develop new treatments for Myasthenia Gravis that restore the function of the synapse with less side effects than current therapies.Read moreRead less
Unveiling The Origin Of Munc18-1 And Alpha-synuclein Co-aggregation At Nanoscale
Funder
National Health and Medical Research Council
Funding Amount
$620,005.00
Summary
Our recent work on Munc18-1 mutations leading to a severe form of human early infantile epileptic encephalopathy (EIEE) led us to uncover a critical role for Munc18-1 in controlling the formation of toxic protein aggregates containing ?-Synuclein. Targeting the Munc18-1 ?-Synuclein interaction may have therapeutic values not only for EIEE but also for other neurological diseases characterised by protein aggregations.
Investigation Into The Intervention Of Arterial Thrombosis And Atherosclerosis Using Shear Sensitive Nanoparticle Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$462,601.00
Summary
In this project we aim to provide a targeted therapy that inhibits atherosclerosis, in-stent restenosis and thrombosis; pathologies characterized by high shear stress due to a reduction in the vessel lumen. We will apply microfluidic technology to characterize lipid nano-capsules that are tagged with antibodies against activated platelets or VCAM-1, loaded with anti-platelet or immune suppressive drugs and are prone to rupture specifically under high shear stress conditions.
Blood clotting is the underlying cause of heart attacks and strokes. We have discovered that the protein, ERp5, is essential for normal blood clotting. Our preliminary findings indicate that ERp5 controls the function of blood platelets in clotting. Our overall aim is to elucidate how ERp5 regulates platelet function. It is crucial that we understand how ERp5 functions in blood clotting if we are to effectively target it in disease.
Viewing The Cellular Responses In Huntington’s Disease Through An Aggreomics Framework
Funder
National Health and Medical Research Council
Funding Amount
$363,218.00
Summary
Huntington disease results from a mutation that causes the Htt protein to form abnormal toxic clusters in neurons that eventually leads to cell death. This project will develop and apply new technology to identify how the clustering process damages cells and will measure all the gene expression changes that occur during the clustering process. The project offers much potential for revealing new therapeutic targets to this incurable disease.
Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
Translating Innovations In Genomic Medicine For Diagnosis And Treatment For Families With Rare Neuromuscular Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Inherited neuromuscular disorders are rare but devastating, affecting a child’s ability to walk or perform activities of daily living, and many are life-limiting. Knowing the faulty gene is vital for families but is often beyond the scope of standard hospital diagnostics. My research uses the latest innovations in genomics to provide a genetic diagnosis for our families, uses cell and animal models to elucidate how diseases occur, and advances new treatments for muscle, heart and brain injury.
PYROXD1 - A Novel Myopathy Disease Gene Identifies A Redox Pathway Essential For Life
Funder
National Health and Medical Research Council
Funding Amount
$1,247,992.00
Summary
An Australian family with a rare myopathy has led to the discovery of a new gene called PYROXD1; a gene that all cells need to survive. PYROXD1 plays a critical role in protecting cells from oxidative stress. We are using patient samples and mouse models to find out what PYROXD1 does that is vital for cell and animal life. We will test whether redox therapies developed for neurodegenerative disorders might help patients with rare neuromuscular disorders, for whom there are no treatment options.