The Role Of The Neuronal Splicing Factor A2BP1 In Autism Spectrum Disorders
Funder
National Health and Medical Research Council
Funding Amount
$396,412.00
Summary
Autism spectrum disorders (ASD) are characterized by language deficits, social impairments and repetitive-restrictive behaviors. ASD is one of the most highly heritable neuropsychiatric conditions, and at the same time genetically very heterogeneous. We have recently shown that shared gene expression abnormalities can be identified in postmortem brain from ASD patients. We now propose to investigate the mechanisms and functional consequences of gene expression abnormalities in ASD.
Approaches To Therapy For The Skeletal Muscle Actin Diseases
Funder
National Health and Medical Research Council
Funding Amount
$912,078.00
Summary
We have shown that errors in a crucial muscle protein called actin cause muscle diseases that affect newborn children. These diseases are mainly very severe, causing death within the first year of life. Currently there is no cure. This project will investigate possible therapies for these diseases, such as viral delivery of a normal version of actin and finding a drug to overcome the weakness. Successful outcomes will crucially bring treatment closer for the patients.
Transforming The Diagnosis Of Mitochondrial Disorders Using High-throughput Sequencing, Functional Prediction And Experimental Validation
Funder
National Health and Medical Research Council
Funding Amount
$670,794.00
Summary
The human genome project sparked enormous improvements in our ability to sequence DNA. “Next Generation” DNA sequencing can potentially sequence an individual’s entire genome in a week and has the ability to transform the diagnosis of inherited diseases but is as yet unproven in a medical genetics context. We will develop and validate the use of Next Generation sequencing to enable the rapid sequencing of over 1000 genes in which mutations cause inherited metabolic diseases.
P2X7 Mediated Phagocytosis Of Apoptotic Cells: A Common Mechanism Underlies Neurological And Eye Disorders
Funder
National Health and Medical Research Council
Funding Amount
$527,033.00
Summary
We have found a strong genetic linkage between a protein called P2X7 and a number of neurological disorders, in line with our recent discovery of a novel function of this protein in clearance of dying cells as removal of unhealthy neurons is essential to keep brain function promptly. Further study using genetic association, cell biology and animal models will lead to a conceptual advance on how neurological diseases are occurred and developed.
In Vivo Analysis Of The Molecular And Neural Mechanism That Underly An Association Of MiRNAs With Mental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$593,778.00
Summary
Genetic studies on autism, schizophrenia, bipolar disorder and major depression suggest that these disorders affect the formation and maintenance of connections between neurons. A group of brain-specific microRNAs, which are regulatory molecules, are predicted to regulate connectivity. Levels of these molecules are found to be abnormal in brains of patients with schizophrenia. This proposal aims to elucidate the function of these microRNAs in the number of neuronal connections, and early motor b ....Genetic studies on autism, schizophrenia, bipolar disorder and major depression suggest that these disorders affect the formation and maintenance of connections between neurons. A group of brain-specific microRNAs, which are regulatory molecules, are predicted to regulate connectivity. Levels of these molecules are found to be abnormal in brains of patients with schizophrenia. This proposal aims to elucidate the function of these microRNAs in the number of neuronal connections, and early motor behavior in transgenic zebrafish.Read moreRead less
The Effects Of ?-actinin-3 On Muscle Metabolism, Human Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
We have identified a common genetic variant that results in absence of the fast muscle fibre protein ?-actinin-3 in more than one billion humans worldwide. Loss of ?-actinin-3 influences elite athletic performance, muscle bulk and strength in the general population, response to diet and exercise, and susceptibility to obesity and developing type 2 diabetes. We have also demonstrated that ?-actinin-3 influence disease severity in a variety of inherited and acquired muscle disorders.
Developing Bone Marrow Transplant And Novel Therapeutic Vectors To Treat Friedreich Ataxia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
We aim to develop effective therapies for the neuromuscular disease Friedreich ataxia (FRDA). The neurodegeneration inherent to FRDA slowly robs a person of the ability to move freely and care for themselves. It needs life-long medical support and there is no cure. FRDA lowers frataxin, a critical mitochondrial protein. Evidence indicates increasing frataxin can be beneficial. Using disease models, we will determine if increasing frataxin via bone marrow transplant or gene therapy improves FRDA.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
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.