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
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.
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
Longitudinal Transcriptome Profiles For People With Dementia
Funder
National Health and Medical Research Council
Funding Amount
$475,913.00
Summary
Over the past decade, less than half a percent of drugs trialled for Alzheimer Disease were found to be effective. This highlights the need for new drug targets. This Fellowship aims to study how genes express themselves over time, among people with very high risk of dementia (genetic form of Alzheimer Disease and Huntington Disease). By looking at gene expression in nerve tissue in the nose, fluid around the brain, and blood, I hope to better understand the disease mechanisms causing dementia.
SELECTIVE VULNERABILITY IN ALZHEIMER’S DISEASE AND RELATED DISORDERS: MECHANISM OF TAU PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$1,072,324.00
Summary
Alzheimer’s disease and related dementias affect 230,000 people in Australia, with numbers expected to grow to 730,000 by 2050. The direct costs for health and residential care alone exceed $6.6 billion per annum. By identifying genes that protect degenerating neurons in the Alzheimer brain, a deeper understanding of the underlying processes will be gained and therapeutic targets will be defined that will assist in developing a therapy for a yet uncurable disease.
From Brain Maps To Mechanisms: Modelling The Pathophysiology Of Dementia
Funder
National Health and Medical Research Council
Funding Amount
$604,513.00
Summary
As the brain ages, the relationship between its structure and function also changes. In this study, I will use detailed computational modelling and extensive analyses of brain dynamics to improve interventional strategies by: 1. Characterising healthy and unhealthy brain dynamics during ageing; 2. Classifying the various subtypes of pathological dynamics; and 3. Predicting pathological neurodegeneration by identifying the earliest signs of perturbations in healthy ageing.
L1 Retrotransposition: The Missing Link Between Genetics And Environmental Factors In Parkinson's Disease ?
Funder
National Health and Medical Research Council
Funding Amount
$604,644.00
Summary
The study proposed here focuses on understanding the role of specific mobile DNA sequences in the interaction between environmental and genetic risk factors causing Parkinson’s disease (PD) leading to dementia. The project proposes identification of mobile DNA induced mutations in post-mortem human PD patient brain samples. The significance and mechanisms of mobile DNA induced mutations will be then tested in a PD mouse model.
Trials of numerous agents to slow the progression of Parkinsons disease have provided ambiguous or negative results despite having good preliminary evidence for their efficacy. The most likely reason is that many nerve cells are already destroyed by the time of diagnosis. Thus effective therapies may be most (and possible only) effective when administered in the presymptomatic stages of disease. This proposal is directed at developing method to detect early presymptomatic Parkinsons disease.
Therapeutic Targeting Of Neuroinflammation To Slow The Progression Of Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
My research has identified key components of our immune system, that can worsen disease in conditions such as Parkinson’s disease and motor neuron disease. I hope that exploring these components in animal models, and patients suffering from these diseases, my group can identify new therapeutic drug candidates that can be progressed in clinical trials. Ultimately, this may lead to new treatments to reduce disease burden in patients suffering from these neurodegenerative conditions.
Restoration Of The Nigrostriatal Pathway In The Parkinsonian Brain
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Many obstacles exist for cell transplantation in Parkinson's disease; namely poor restoration of the host brain circuitry due to incorrect graft placement. This results in incomplete motor function and unwanted side effects. Through iterative studies we endeavor to restore this circuitry by placing grafts in the appropriate location and promoting their survival and growth-integrations. This will require: optimizing the donor tissue and exposure of the graft to growth stimulating factors.