Dysferlin And The Emergency Vesicle Fusion Of Membrane Repair
Funder
National Health and Medical Research Council
Funding Amount
$481,496.00
Summary
Membrane repair is a vital cell survival mechanism of all eukaryotic cells, using calcium-triggered vesicle fusion to ‘patch’ membrane ruptures. The muscular dystrophy protein dysferlin is a key mediator of membrane repair, although, exactly how dysferlin mends membranes has been unclear. We show that the calcium that floods through membrane tears, activates a group of enzymes called calpains, that specifically cleave dysferlin to release a specialist vesicle-fusion module for membrane repair.
The Identification Of Novel Genetic Loci And Pathways Associated With ALS Through Interrogation Of Multiple Integrated Genomics Data Sets
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
In 85% of amyotrophic lateral sclerosis (ALS) cases the causative mutation is not known. Here, we will use novel genomics and molecular methods to improve diagnosis and enhance the understanding of severe neuronal degeneration. This includes the characterisation of patient neurons to fast-track genetic discovery with patient-specific treatment assays. We envisage an expanded diagnostic and treatment suite that will provide answers for all ALS patients for whom there is no known genetic cause.
Epilepsy is a debilitating neurological disorder characterised by spontaneous seizures. For a third of epilepsy patients, drugs cannot prevent epileptic seizures from occurring without causing severe side effects. Therefore alternative treatments are needed. This work will develop epileptic seizure warning methods. This will alleviate the stress of randomly occurring seizures by giving patients the chance to move to safety before a seizure occurs, therefore enhancing their quality of life.
Protein Disulphide Isomerase And Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$307,524.00
Summary
Motor Neuron Disease (MND) patients currently face a bleak future. In the common global form of disease, the average length of survival after diagnosis is 31 months. Current therapies have at best a modest effect on the course of the disease with little or no benefit in terms of overall patient survival. We have new evidence that a protein called PDI can prevent the motor neuron cells from dying in MND and hence this may be a novel therapeutic target for both sporadic and familial forms of MND.
Determining The Genetic Control Of Corpus Callosum Development
Funder
National Health and Medical Research Council
Funding Amount
$625,800.00
Summary
Disorders of early brain development are significant causes of illness and disability in children, who present with a number of clinical problems including delayed development, seizures, weakness and learning difficulties. The cause of these conditions remains poorly understood, however it is emerging that genes play a key role. This project will identify and characterise novel genes associated with abnormal brain development and identify new potential targets for treatment.
ALS4 Mice Show TDP-43 Protein Mislocalization In Motor Neurons Characteristic Of Sporadic ALS Patients; Suggesting This Model Is Likely To Reveal Important Patho-mechanistic Disease Insights
Funder
National Health and Medical Research Council
Funding Amount
$108,466.00
Summary
SETX gene mutations cause an inherited motor neurone disease (MND) known as ALS4. Our current understanding of MND was revolutionized by the discovery that a protein known as TDP-43 is the main component of protein accumulations found in dying human motor neurones. We have generated a unique mouse model of ALS disease that will be useful for research purposes, but may also prove effective for drug testing.