I aim to decipher the role of heritable, genetic DNA variation in human neurological disease. I will use next generation genomics technologies together with sophisticated cellular models to address the important questions of the biology of epilepsy and intellectual disability in particular. I aim to develop a treatment for a specific type of epilepsy, which affects only girls from the age of 6 months. My ultimate goal is to improve the life of the patients and their relatives.
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
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.
Epilepsy is a very common and serious brain disorder. Epilepsy often includes other disabilities, reduction in quality of life and is associated with increased risk of early death. 30% of people with epilepsy are unable to gain control of their seizures with currently available medications. The genetic causes of the large majority of epilepsy cases have not yet been found. This project aims to identify new genetic causes of epilepsy and its related disorders.
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.
Cell Type Specification In Developing CNS: Functional Analysis Of Sox14
Funder
National Health and Medical Research Council
Funding Amount
$468,055.00
Summary
The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are ....The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are maintained in the adult. This has been largely due to a lack of efficient and reliable methods to identify and study interneurons. We have previously discovered that a gene termed Sox14 is active in distinct interneuron groups in the embryonic brain and spinal cord. Sox14 is a member of the Sox gene family, many of which act as genetic switches to control cell and tissue development. We found that Sox14 has been extremely well conserved throughout evolution and is active in similar interneuron groups in a number of animal species. These studies led us to hypothesise that Sox14 controls a critical molecular step in the generation of certain interneurons that may be involved in reflexes, locomotion or motor coordination. In this project, we will investigate both the role of Sox14 in interneuron development and the functions of interneurons in which this gene is active. We will do so by combining modern molecular and genetic techniques with physiological approaches. This project will reveal critical molecular steps in CNS development and determine the functions of a specific group of interneurons. To this end, we will generate mouse strains in which a specific group of interneurons are genetically marked and can be manipulated during development. We envisage that these mice with 'modified brain circuits' will become unique resources for future investigations of selected interneuron types and their functions.Read moreRead less
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