The Role Of The Gtf2i Gene Family In Behaviour And Williams Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$629,396.00
Summary
Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic ....Williams Syndrome (WS) is a complex neurodevelopmental disorder in humans caused by a deletion of 21 genes on chromosome 7. This results in a reduced IQ and marked visuospatial deficiencies. However, unlike other forms of mental retardation, some important cognitive abilities are completely normal. WS patients show normal development of linguistic abilities and anecdotal evidence suggests they possess an above average musical ability. In addition, these individuals also possess a characteristic overfriendly, gregarious personality with little inhibition towards strangers. Such a characteristic cognitive and behavioral profile in a genetic disorder has provided convincing evidence that genes play a role in specifying cognitive abilities and behavior. This interesting syndrome gives us an insight into the perplexing debate of Nature vs Nurture. It also provides a unique and invaluable opportunity to dissect the role of certain genes in complex neurodevelopmental pathways that result in cognition and behavior. Recently, patients with smaller (atypical) deletions of genes in the WS region have been described. These patients do not display the full 'classical' range of WS characteristics. The identification of which genes are deleted in these patients suggests that two genes in particular, GTF2IRD1 and GTF2I, are involved in visuospatial abilities, sociability and specific anxieties and phobias. Our laboratory was the first to identify proteins encoded by GTF2IRD1, known as MusTRDs, that act for the most part to suppress gene expression. Furthermore, our laboratory has been studying a mouse model in which the Gtf2ird1 gene has been deleted, similar to the situation in WS, and have found that the mice are more 'social' and exploratory. In this project, we want to determine if other behavioural features of WS are contributed to by this gene and-or its related gene, Gtf2i, and to characterize the role that these genes play in neuronal cell function.Read moreRead less
Identification And Characterisation Of A Novel Parkinson's Disease Gene
Funder
National Health and Medical Research Council
Funding Amount
$556,313.00
Summary
Parkinson’s disease (PD) is a complex neurological condition affecting 100,000 Australians. The primary clinical features of PD result from the selective loss of a specific type of neuron. These neurons make up less than 1% of the over 50 million neurons within the brain, and it is currently unclear why they are preferentially lost during disease development. We have identified a novel gene that causes early onset parkinsonism. This study will characterise the gene and determine what role it pla ....Parkinson’s disease (PD) is a complex neurological condition affecting 100,000 Australians. The primary clinical features of PD result from the selective loss of a specific type of neuron. These neurons make up less than 1% of the over 50 million neurons within the brain, and it is currently unclear why they are preferentially lost during disease development. We have identified a novel gene that causes early onset parkinsonism. This study will characterise the gene and determine what role it plays in the development of PD.Read moreRead less
Viral-mediated Modulation Of BDNF Expression In Motor Neurons To Promote The Recovery Of Hand/digits Function In A Rat Model Of Spinal Cord Injury That Impairs Normal Grasping Action.
Funder
National Health and Medical Research Council
Funding Amount
$341,427.00
Summary
This project seeks to lure injured axons towards motor neurons, a process that is essential for the recovery of motor function. BDNF gradients will be created along the injured axons path. Axons will have to elongate to reach the first source of BDNF. They will need to elongate even more to get to the next source of BDNF, hence bringing them each time closer to their lost targets. This gene therapy scenario has the potential to bring gene therapy a step closer for human spinal cord injury.
We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being pas ....We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being passively deflected by objects. Deflection results in inputs to the brain that are processed to form the neural basis for very finely detailed perceptual behaviour. In rats, with impoverished visual and auditory senses, the whiskers are the major sensory system for interacting with the world, and are used in navigating the environment and in finding and distinguishing foods. Thus they contribute strongly to the remarkable success of this species. This elegant sensory system has a number of advantages that make it a very good model for the study of brain mechanisms responsible for active fine-grain sensory function. We plan to take advantage of the unique features of this system to define the information processing that occurs in the cortex in this elegantly complex system. This will address an issue relevant to all sensory systems - namely the neural basis of complex fine grain perceptual behaviour. Understanding the mechanisms underlying active tactile perception also has relevance to clinical conditions involving deficits in active touch e.g., in diabetic polyneuropathy (which eventually affects ~50% of diabetics), in leprosy (in which an early sign is damage to active touch). Knowledge of the core brain processes in active touch gained in this study could eventually underpin the ameliorative technologies for such deficits.Read moreRead less
Neurodevelopmental Role Of Susceptibility Genes For Autism Spectrum Disorders: From Genes To Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$482,968.00
Summary
Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better unders ....Autism is a developmental neuropsychiatric syndrome characterised by impairments in three principal domains: social interaction, language and behavioural inflexibility. Autism spectrum disorder (ASD) refers to a group of neurodevelopmental syndromes with the common feature of dysfunctional reciprocal social interaction. In this project we will investigate the role of genes that increase the risk of ASD in the development of behaviours using an animal model. This work will lead to a better understanding of the genetic basis of ASD.Read moreRead less
Control Of Prosthetic Limbs From Decoded Brain Signals
Funder
National Health and Medical Research Council
Funding Amount
$895,832.00
Summary
This research will restore mobility to patients who suffer from paralysis. We aim to create a device, known as a brain-machine interface, which is an artificial communication path from the brain that bypasses an injury, such as a damaged spinal cord or stroke. The interface will decode a user’s intent and act upon it. Decoders will use physiological principals and state-of-the-art machine learning methods. We will test a user’s ability to control an artificial limb using decoded brain activity.
Characterisation And Modelling Of Schizophrenia-associated Dysregulation Of MiR-137 Expression
Funder
National Health and Medical Research Council
Funding Amount
$581,661.00
Summary
We have identified mutation-associated changes in the expression of a non-coding microRNA gene in the cerebral cortex in schizophrenia. This gene, known as MIR137, functions by repressing hundreds of target genes and therefore has major implications for schizophrenia. The project will identify the genetic mechanism affecting the expression of MIR137, and determine the biological and behavioural implications of this change in the context of schizophrenia.
Epistatic Genetic Effects On Neuroanatomical Subtypes Of Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$410,141.00
Summary
Schizophrenia represents a number of clinically distinct syndromes, with a complex mode of inheritance. The delineation of biologically valid subtypes of schizophrenia is necessary to advance our understanding of the genetic basis of these syndromes. This project uses pattern classification techniques to determine subtypes of schizophrenia on the basis of structural brain abnormality across multiple regions, and will examine genetic interactions and differential gene expression associated with t ....Schizophrenia represents a number of clinically distinct syndromes, with a complex mode of inheritance. The delineation of biologically valid subtypes of schizophrenia is necessary to advance our understanding of the genetic basis of these syndromes. This project uses pattern classification techniques to determine subtypes of schizophrenia on the basis of structural brain abnormality across multiple regions, and will examine genetic interactions and differential gene expression associated with these biologically-derived subtypes.Read moreRead less
Advancing The Evidence-base For Childhood Brain Insult: Diagnosis, Assessment And Intervention
Funder
National Health and Medical Research Council
Funding Amount
$575,662.00
Summary
My research has 4 primary objectives, representing major gaps in current knowledge: 1. improve knowledge of recovery and determinants of post-concussive symptoms 2. establish the impact of child brain insult on socio-emotional function and identify contributing factors 3. develop an iPad based tool for socio-emotional function 4. evaluate and disseminate e-heath treatments for child brain insult
Novel Methods To Study Structural-functional Connectivity In Epilepsy And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$697,605.00
Summary
Magnetic Resonance Imaging (MRI) is a non-invasive method that has revolutionised our understanding of clinical neuroscience. MRI provides not only high-contrast anatomical images, but also information on brain physiology and function. My primary goal is to develop and optimise novel MRI methods for a more accurate measure of brain structure and function. My research program will focus on the application of these methods to the investigation of epilepsy and schizophrenia.