Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to suscept ....Molecular dissection of the effects of alpha-actinin-3 deficiency on normal variation in skeletal muscle function. We will study the mechanisms by which a common genetic variant influences muscle bulk, muscle strength and the metabolic efficiency of muscle in the general population. Common genetic variants that influence skeletal muscle function have major potential public health implications as they are likely to influence individuals' response to exercise and diet, and to contribute to susceptibility to common diseases such as obesity, diabetes, and the loss of muscle strength in the elderly. In addition, the identification of genetic factors that influence muscle bulk in vertebrates has implications for breeding programs in sheep and cattle and may provide commercial benefit to the livestock industry.Read moreRead less
Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understandin ....Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understanding of olfaction in insects, increased national and international collaboration, and outstanding graduate student training. This research will be of significant future benefit in deriving methods to modify the behaviour of insects of agricultural or medical importance, for example the sheep blowfly. Read moreRead less
Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general ....Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general population.Read moreRead less
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