Identifying Disease Genes For Neurogenetic Disorders Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$2,523,023.00
Summary
This project aims to identify novel disease genes, in other words, find genes, which have not previously been shown to cause human diseases when they are mutated. The collaborating laboratories on the project in Perth, Sydney, Melbourne and Boston, USA have a successful history in working together in finding human disease genes, harnessing, in the last few years, the now readily available power of next generation DNA sequencing to accelerate disease gene discovery.
Neuromuscular Disorders: Gene Discovery And Disease Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$880,569.00
Summary
Inherited muscle disorders lead to lifelong disability and early death. Less that 50% of patients get an accurate diagnosis and there are currently no effective therapies. In this project, two leading Australian laboratories will use state-of-the-art methods to identify novel disease genes and how they cause muscle weakness. This research will have immediate outcomes to diagnosis, management and prevention and for the development of new therapeutic agents.
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.
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder, with one Australian dying from ALS every day. The mechanisms underlying the development of ALS remain to be determined. Using a novel neurophysiological technique, it is envisaged that the current proposal will establish that ALS begins in the brain and is mediated by cortical hyperexcitability. Further, a diagnostic test for ALS will be developed ensuring earlier diagnosis and institution of treatment.
Investigation Of The Function Of The Scaffolding Protein LIN-2/CASK In Cholinergic Synapses
Funder
National Health and Medical Research Council
Funding Amount
$911,656.00
Summary
Scaffolding proteins play vital role in synapses to maintain the function of the nervous system. One important scaffolds LIN-2/CASK has been implicated in autism disorders and has profound effect on synaptic function. Here we investigate the function of LIN-2/CASK and its binding partners in cholinergic synapses to dissect how they regulate synaptic transmission.
DHPR ? Subunit Binding To A Variably Spliced Region Of RyR1: A Role In EC Coupling And Myotonic Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
We have uncovered a communication pathway between two ion channel molecules in muscle cells that underlies human movement. The pathway is critical in normal mobility and is disrupted in myotonic dystrophy. We will study the molecular components of this pathway to understand normal body function and abnormal function in mytotonic dystrophy. The work will facilitate the design of drugs to relieve the mytotonic dystrophy myopathy and form new and much needed class of specific muscle relaxants.
Neuromuscular Junction Toxicity After Anticholinesterase Pesticide Poisoning And Envenomation.
Funder
National Health and Medical Research Council
Funding Amount
$1,351,392.00
Summary
The study builds on strong existing NHMRC funded collaborative research links between Sri Lanka and Australia in research which have reduced mortality and provided better evidence for treatment of pesticide poisoning. We will study the paralysing effects of acute insecticide poisoning and snakebite on the human nervous system. We aim to determine whether these can be predicted early in the course of the illness and the long term effects. We also aim to see if any particular insecticides cause mo ....The study builds on strong existing NHMRC funded collaborative research links between Sri Lanka and Australia in research which have reduced mortality and provided better evidence for treatment of pesticide poisoning. We will study the paralysing effects of acute insecticide poisoning and snakebite on the human nervous system. We aim to determine whether these can be predicted early in the course of the illness and the long term effects. We also aim to see if any particular insecticides cause more problems than others.Read moreRead less
Circuit Class Therapy For Rehabilitation Clients. A Pragmatic Randomized Controlled Trial Of Therapy Intensity (CIRCIT).
Funder
National Health and Medical Research Council
Funding Amount
$526,361.00
Summary
Loss of independence is common after stroke, and may lead to reduced quality of life and admission to nursing home care. We will investigate if an increased amount of rehabilitation following stroke leads to improved mobility. Two ways of delivering more intense rehabilitation will be compared with usual care to find out which leads to improved physical mobility, and how they compare economically. This will allow health service providers to optimise services and will benefit people with stroke.
How The Environment And Epigenetics Affect The Brain Disease Gene, MAPT.
Funder
National Health and Medical Research Council
Summary
Genetic variants in the microtubule associated protein Tau (MAPT) gene are major risk factors for Alzheimer’s disease and Parkinson’s disease. Environmental or lifestyle factors, such as diet and smoking, have crucial roles in changing the risk of developing these diseases. These environmental factors may exert their influence via a mechanism known as "epigenetics". This project aims to determine whether the MAPT gene is susceptible to epigenetic changes by environmental factors, and whether thi ....Genetic variants in the microtubule associated protein Tau (MAPT) gene are major risk factors for Alzheimer’s disease and Parkinson’s disease. Environmental or lifestyle factors, such as diet and smoking, have crucial roles in changing the risk of developing these diseases. These environmental factors may exert their influence via a mechanism known as "epigenetics". This project aims to determine whether the MAPT gene is susceptible to epigenetic changes by environmental factors, and whether this process will have an impact on these diseases.Read moreRead less
Defining The Changes In Cell Biology Caused By PRESENILIN Truncations Associated With Different Diseases
Funder
National Health and Medical Research Council
Funding Amount
$622,886.00
Summary
Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be requir ....Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be required for the development of treatments.Read moreRead less