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.
Defining The Role Of Inflammation In Depression During Aging
Funder
National Health and Medical Research Council
Funding Amount
$736,820.00
Summary
This proposed research investigates the bidirectional relationship between inflammation in the central nervous system (CNS) and depression during normal aging processes. It is assumed that inflammatory processes in the CNS will induce the development of depression and vice versa, that depression will lead to increased inflammation in the body. In addition, the research will study the genetic background and gene expression of inflammation contributing to both aging processes and the onset of depr ....This proposed research investigates the bidirectional relationship between inflammation in the central nervous system (CNS) and depression during normal aging processes. It is assumed that inflammatory processes in the CNS will induce the development of depression and vice versa, that depression will lead to increased inflammation in the body. In addition, the research will study the genetic background and gene expression of inflammation contributing to both aging processes and the onset of depression during aging.Read moreRead less
Problems in learning, memory and other complex mental processes are common to many brain disorders. This project will study the impact of mutations on a family of genes reported in autism and schizophrenia, on complex cognitive behaviours using novel behavioural technologies. This will not only shed fundamental insights into the specific mental processes regulated by these genes and their role in disease, but importantly provide novel targets for the development of therapies.
Investigation Of Neuregulin Precessing By Beta-site APP Cleaving Enzyme And Gamma Secretase In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$46,715.00
Summary
Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more s ....Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more selective therapies with less side-effects.Read moreRead less
Defining The Changes In Cell Biology Caused By PRESENILIN Truncations Associated With Different Diseases
Funder
National Health and Medical Research Council
Funding Amount
$622,886.00
Summary
Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be requir ....Truncations of the PRESENILIN genes in humans can cause two very different diseases: inherited, early onset Alzheimer’s disease (familial Alzheimer's disease) and a skin disease named inherited Acne Inversa. One truncation is also involved in the non-inherited, late onset form of Alzheimer’s disease. Why do these different truncations produce different diseases? Investigating this question will teach us more about the molecular bases of these different diseases. This understanding will be required for the development of treatments.Read moreRead less