To Investigate The Role Of ATM Protein In Protecting Against Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$953,662.00
Summary
The overall aim of the project is to employ a rat model to investigate neurodegeneration in patients with ataxia-telangiectasia (A-T). Ataxia-telangiectasia is a complex multisystem disorder characterised by progressive neurological impairment, variable immunodeficiency and cancer predisposition. The rat model recapitulates the neurodegeneration in patients and thus this project will provide important insight into the nature of the defect as well as approaches for the treatment of the disorder.
The Leucine Rich Repeat Kinase 1 And 2 Genes Are Modulators Of Alternative Splicing - Implication For Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$583,809.00
Summary
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two common causes of dementia and neurodegeneration. Through positional cloning, we have identified the leucine rich repeat kinase (LRRK1) 1 gene as a modulator of alternative splicing. We have subsequently shown that its homologue, LRRK2 has a similar biological activity. We propose to study the the genetic and biochemical role of LRRK1 and LRRK2 in neurodegeneration in terms of its effect in splicing.
Functional Genomics-new Technologies For Gene Discovery And Personalised Medicine
Funder
National Health and Medical Research Council
Funding Amount
$452,122.00
Summary
Disorders of the brain, which affect people of all ages, are one of the largest health, economic and social burdens in the developed world. These conditions are chronic, debilitating and have limited symptomatic treatments available. In general, very little is known about the causes of many brain disorders. This project aims to identify the genes and mechanisms that underlie these diseases to enable the development of diagnostic and treatment programs to help reduce the incidence and severity of ....Disorders of the brain, which affect people of all ages, are one of the largest health, economic and social burdens in the developed world. These conditions are chronic, debilitating and have limited symptomatic treatments available. In general, very little is known about the causes of many brain disorders. This project aims to identify the genes and mechanisms that underlie these diseases to enable the development of diagnostic and treatment programs to help reduce the incidence and severity of disease.Read moreRead less
Biological Characterisation Of The Opiod Receptor Sigma 1 Gene In The Frontotemporal Dementia And Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$480,211.00
Summary
Frontotemporal dementia (FTD) and motor neuron disease (MND) are the two common causes of dementia and neurodegeneration. We have identified a new genes that causes familial FTD and MND in pedigrees affected with dementia and-or MND.This project will study the expression and function of this new FTD-MND gene to determine its role in the aetiology and pathology of this complex of neurodegenerative disorders.
Decoding Mechanisms Of Brain-intestinal Communication
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Obesity is a worldwide concern to human health. Research into how fat is regulated in the body may provide new therapeutic options. It is not well understood how signals from the brain control fat storage. We have recently identified a gene that is important for the communication between the brain and the intestine in the control of fat levels. As such, our work will enable us to better understand this phenomenon.
PArkin Co-Regulated Gene (PACRG), Parkin And Parkinsonism.
Funder
National Health and Medical Research Council
Funding Amount
$397,740.00
Summary
Parkinson's disease (PD) is a common neurodegenerative disorder affecting greater than two percent of individuals over the age of 65. The disease is characterised by tremor, slowness of movement, rigidity and postural instability. Current treatment regimes may provide some measure of symptomatic relief, but currently there is no treatment to halt or slow the progression of this debilitating disease. PD currently affects an estimated 35,000 people in Australia and this figure is predicted to incr ....Parkinson's disease (PD) is a common neurodegenerative disorder affecting greater than two percent of individuals over the age of 65. The disease is characterised by tremor, slowness of movement, rigidity and postural instability. Current treatment regimes may provide some measure of symptomatic relief, but currently there is no treatment to halt or slow the progression of this debilitating disease. PD currently affects an estimated 35,000 people in Australia and this figure is predicted to increase significantly as the population ages. PD is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause PD when disrupted. We have identified a new gene that we believe may be involved in PD. The overall aim of this proposal is to characterise this gene and what role it plays in the development of PD. Understanding the expression and function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model Parkinson's disease in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in PD and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less
Investigating The Role Of The UPF3B Gene And Nonsense Mediated RNA Decay (NMD) Process In Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$572,710.00
Summary
Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes c ....Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes causing various forms of intellectual disability. Surprisingly the number of genes, in which mutations cause various forms of intellectual disability is unexpectedly high. Just on the human X-chromosome we expect in excess of 200 such genes, which is nearly 30% of the gene content of this chromosome. We propose to study a novel gene, UPF3B, we recently identified to be mutated in a form of intellectual disability. The normal function of this gene and its protein is known to a certain extent. The UPF3B protein plays a role of a guardian of other genes in human (and also other species) cells. The role of the UPF3B protein is to prevent erroneous genetic information to be used for the building of proteins with potentially toxic effects to the organism. In our patients this process clearly malfunctions as a consequence of the damaged UPF3B gene. We propose to shed some more light in to the molecular intricacies of this process with the aim to better understand the mechanics of the process. Families, which participate in our studies and have this gene involved will benefit from the availability of direct test. Multiple other families around the world are also likely to benefit, now or in the future.Read moreRead less
Identifying Mitochondrial Genome Variants Associated With Familial Migraine Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$443,273.00
Summary
New therapeutic targets for migraine are desperately needed. Although studies have identified some migraine genes there remains considerable underlying genetic variation to be characterised. This study aims to identify functional variants in the mitochondrial genome that contribute to migraine susceptibility, utilising the isolated Norfolk Island population. Outcomes will determine the significance of the variants identified, potentially leading to new diagnostics.
Identifying Novel Gene Mutations For Molecular Diagnosis Of Familial Hemiplegic Migraine
Funder
National Health and Medical Research Council
Funding Amount
$623,460.00
Summary
This proposal aims to identify novel FHM genes by undertaking an NGS screen of the whole exome of 209 FHM patient samples. We will test the pathological relevance of detected novel mutations by functional analysis in human cell models and using patient-specific stem cell techniques. Using whole genome NGS technology to identify novel mutations will assist in the design and development of a comprehensive NGS approach to diagnose and differentiate this severe neurological disorder.
This study is aimed at identifying genetic variants that influence susceptibility to migraine. We plan to use DNA samples already collected from families with multiple migraine affected individuals and sequence a region on the X chromosome that has previously been identified as harbouring a migraine susceptibility gene. This project will identify gene(s) that contain variants contributing to migraine.