Characterisation Of Eating Behaviour And Metabolic Phenotypes Across Neurodegenerative Diseases: Insights For Survival And Progression
Funder
National Health and Medical Research Council
Funding Amount
$340,891.00
Summary
It has been suggested that metabolic changes and eating behavior could modify the progression of neurodegeneration. This research aims using brain imaging, pathological examination and novel techniques from obesity research to examine if there are characteristic metabolic changes in patients with frontotemporal dementia, Amyotrophic lateral sclerosis and Alzheimer’s disease; how these changes relate to eating behavior, and how they may affect disease progression and survival.
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.
Novel Pathomechanisms And Therapeutic Targets In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$340,038.00
Summary
This fellowship will provide new insight into the molecular processes underlying onset and progression of common brain conditions, including Alzheimer’s disease, frontotemporal dementia and motor neuron disease. Furthermore, new therapeutic targets for these diseases will be developed and tested in model systems, to facilitate future translation into clinical application, and to overcome the lack of treatments.
Mechanisms Of Cortical And Respiratory Degenerations In Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$333,900.00
Summary
This study will be the first to chronicle how and when motor neurons (MNs) in the brain and spinal cord degenerate before, during and after ALS symptoms in 2 different mouse models. The MNs studied control breathing muscles and are a key disease progression and mortality indicator in patients. I expect drastic shape and electrical abnormalities, providing information useful to clinicians about how and when brain and spinal cord MNs degenerate, uncovering new therapeutic targets and time-points.
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
Astrocytic Contributions To Tissue Damage And Dysfunction In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$275,810.00
Summary
Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to o ....Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to open up new avenues for ameliorating damage and improving outcomes for stroke patients. Astrocytes are one of the major populations of cells in the brain. They play key roles in supporting normal brain function and protecting nerve cells in the brain. Because of their many functions, these cells offer considerable potential as a therapeutic target in stroke. Unfortunately, the responses of astrocytes in this disorder are poorly understood due partly to a lack of techniques to distinguish their contributions from that of other cells in the brain. We have recently designed a novel system using antibodies to deliver genes into selected populations of nerve cells in the nervous system and thus to selectively alter the function of these cells. In the proposed study, we will adapt this technique to selectively modify gene expression in astrocytes. We will then apply the procedure to determine the consequences of altering key functions in astrocytes on the brain damage and behavioural changes that develop in an animal model of stroke. The successful completion of this research will provide a powerful means to investigate the function of astrocytes, not only in diseases such as stroke but also in normal brain. We will also gain novel insights into the astrocytic role in the damage and dysfunction resulting from stroke that have potential applications in developing new therapies.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
Molecular Control Of Interneuron Development And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$527,828.00
Summary
This project will study the changes that occur in neurons, during normal brain maturation and in pathology. We hypothesise that early signs of brain malfunction can be detected in neurons before symptoms appear. The role of a gene will be studied during development and disease in a mouse model of autism, in order to identify the molecular and electrical signs of abnormal activity. This research will ultimately enable us to propose new strategies to treat symptoms of brain disease.
Biomaterials For The Direct Reprograming Of Reactive Astrocytes Into Functional Neurons
Funder
National Health and Medical Research Council
Funding Amount
$630,500.00
Summary
We will employ peptide inspired hydrogel nanoscaffolds that can be injected into a brain lesion as a single injection to provide chemical and physical support for the surrounding cells. We will utilize various modifications to these materials to reprogram inflammatory cells into neurons, whilst also promoting the survival, maintenance and growth of existing neurons to encourage repair.