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
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
Developing Novel Selective Glycine Receptor Potentiators As A Means To Control Pain.
Funder
National Health and Medical Research Council
Funding Amount
$552,647.00
Summary
It has been estimated that >3M Australians suffer from pain at a cost to the economy of >$34B, with chronic pain (persisting beyond 1-6 mths) accounting for ~half this burden. There is an urgent and compelling social and economic case for the development of safer and more effective pain therapeutics. This project takes inspiration from a new class of Australian marine natural products that selectively regulate a key pain pathway, and will optimize and develop these as a new class of pain d ....It has been estimated that >3M Australians suffer from pain at a cost to the economy of >$34B, with chronic pain (persisting beyond 1-6 mths) accounting for ~half this burden. There is an urgent and compelling social and economic case for the development of safer and more effective pain therapeutics. This project takes inspiration from a new class of Australian marine natural products that selectively regulate a key pain pathway, and will optimize and develop these as a new class of pain drug.Read moreRead less
Therapeutic Potential Of Glycine Receptors In Pain Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$292,223.00
Summary
Inflammation caused by infection or injury leads to a heightened sensation of pain and can convert non-painful stimuli (e.g., touch) into painful stimuli. This effect is mediated by the production of prostaglandins both in peripheral tissues and in the spinal cord. Prostaglandins have recently been shown to decrease the magnitude of the inhibitory neurotransmission that normally occurs onto pain sensing neurons in the spinal cord. This has the effect of raising the excitability of these neurons, ....Inflammation caused by infection or injury leads to a heightened sensation of pain and can convert non-painful stimuli (e.g., touch) into painful stimuli. This effect is mediated by the production of prostaglandins both in peripheral tissues and in the spinal cord. Prostaglandins have recently been shown to decrease the magnitude of the inhibitory neurotransmission that normally occurs onto pain sensing neurons in the spinal cord. This has the effect of raising the excitability of these neurons, thereby making it easier for weak pain stimuli to be relayed to the brain. Inhibitory neurotransmission onto pain sensing neurons is largely mediated by the alpha3 glycine receptor subunit that is not found anywhere else in the body. Very little is known about the physiological and pharmacological properties of these receptors. We hypothesise that drugs that increase the activation of alpha3 glycine receptors may provide a novel treatment for pain. This project will firstly identify new drugs that can increase the activation of these receptors. It will then test whether these drugs are likely to work in vivo. The project will also establish why these receptors are found only on pain neurons. Together, this information will establish whether alpha3 glycine receptors represent a promising new therapeutic target for inflammatory pain, and will place us in an excellent position to begin the next step of identifying novel therapeutic lead compounds.Read moreRead less
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
Controlling The Development And Function Of Hindbrain Commissures In Vertebrate Animals: The Role Of Robo3 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$393,834.00
Summary
Commissural axons connect and coordinate activity between neurons of the left and right sides of the central nervous system. In the forebrain, formation of commissural axons is determined by guidance factors at the midline between the two hemispheres, and abnormalities in guidance can cause developmental malformations. The aims of this project are to elucidate function of the Robo/Slit family of molecules in regulating axon guidance of commissural neurons, particularly in the corpus callosum.
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.
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.