Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS rese ....Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS research including epidemiology, immunology and neurobiology. Collaboration of 8 major Australian institutions is also important for this project and future studies. The team will have access to a new national MS GeneBank (platform) with samples from 2240 patients that should generate findings important to world-wide MS genetic knowledge.Read moreRead less
The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themse ....The Genetic Analysis of Neurological Diseases. Multiple sclerosis and Parkinson's are debilitating neurodegenerative diseases, which affect 16,000 and 80,000 Australians, respectively. Between them, these diseases cost the community $7.8 billion per annum, and there is no cure. This proposal will study the genes that influence a person's predisposition to developing these diseases, and what makes some people have particular characteristics. It will provide novel insights into the diseases themselves and information that could help in the development of new and more effective drugs, and biomarkers to assist in the prediction of prognosis. Such advances would decrease the economic impact of these diseases and improve quality of life for those affected.Read moreRead less
New tools to activate and silence neural circuits. Many neurological disorders occur as a result of neuron cell death that is initiated by excessive levels of excitatory activity in central nervous system neurons. This project will develop and validate a new treatment for these disorders that involves silencing excessive neuronal activity using a safe, commonly prescribed drug.
Brain sodium channel: functional role of developmentally regulated alternative splicing. This project will identify the roles of neonatal and adult forms of a sodium channel in the function of neurons in the developing brain. Sodium channels are vital for brain function and this study will improve our understanding of the function of healthy brain as well as of underlying mechanisms of some neurological disorders.
Gene-environment interactions mediating experience-dependent plasticity in the healthy and diseased brain. The aim of this project is to understand how genes and environment combine to affect susceptibility to various brain disorders, using models of human diseases and manipulating environmental factors such as mental and physical activity. The project's focus is on neurological and psychiatric disorders, including Huntington's disease, depression, schizophrenia and autism.
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.