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Mechanisms Underlying Generation Of Febrile Seizures In Mouse Models Of Human Familial Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$304,559.00
Summary
Febrile Seizures (FS) affect 3% of children aged 0.5 - 6 yrs and have been proposed as an indicator of severe forms of adult generalized epilepsy. Mechanisms underlying FS generation are unknown although studies of Australian families suffering from epilepsy have linked 2 genes to FS. We have generated mice expressing these 2 genes. Aims and Outcomes: to investigate events triggering FS which will provide important insights into why FS occurs in children. (NB: CIA 2 yr career interruption)
Alzheimer's Disease And Dementia With Lewy Bodies: How Different Are They?
Funder
National Health and Medical Research Council
Funding Amount
$565,500.00
Summary
Dementia is a devastating disorder, taking the individuals mind. As the population ages, a significant proportion become demented, impacting on these individuals, their families and the community as a whole (Federal and State budgets for this disorder are costed in the billions). There are many cellular causes of dementia, the most frequent being considered Alzheimer's disease. However, many people currently thought to have Alzheimer's disease have another dementia cause - dementia with Lewy bod ....Dementia is a devastating disorder, taking the individuals mind. As the population ages, a significant proportion become demented, impacting on these individuals, their families and the community as a whole (Federal and State budgets for this disorder are costed in the billions). There are many cellular causes of dementia, the most frequent being considered Alzheimer's disease. However, many people currently thought to have Alzheimer's disease have another dementia cause - dementia with Lewy bodies. This study aims to determine 1) how common these two types of dementias are (currently unknown) 2) how better to diagnose them and tell them apart 3) how badly the brain is affected by each disorder and 4) whether the same genes are involved in both disorders. The knowledge we will gain will allow better diagnosis of the cellular causes of dementia, knowledge necessary for rational treatment.Read moreRead less
Visualisation Of Functionally Activated Circuitry In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
We are seeking to develop a method to precisely determine which parts of the brain are involved in the carrying out of different brain functions. The main advantage of our new method will be that we will be able to directly visualise the circuitry involved in a specified brain function. The brain is like a vast computer, with literally billions of connections between different parts, and it is these connections which are used to form functional circuits, which ultimately result in the brain cont ....We are seeking to develop a method to precisely determine which parts of the brain are involved in the carrying out of different brain functions. The main advantage of our new method will be that we will be able to directly visualise the circuitry involved in a specified brain function. The brain is like a vast computer, with literally billions of connections between different parts, and it is these connections which are used to form functional circuits, which ultimately result in the brain control of bodily function. Up until now, there has been no direct way of being able to directly visualise which of those billions of connections are involved in the formation of a circuit for any particular brain function. We plan to use a genetic approach to help to visualise functionally activated brain circuits. We know that some genes are turned on in the nerve cells which are activated during a brain function. We will use this knowledge to generate a new line of genetically engineered mice. In these mice, the genes which are turned on during brain activation will in turn be used to turn on special markers which will light up the activated circuits. This will be of great signficance in our understanding of brain function. It should also help us to understand what happens to these circuits in different diseases of the brain, such as following stroke, in senility, and Alzheimer's disease.Read moreRead less
Characterization Ol A Novel Covalently Cross -linked Abeta Peptide Dimer And Its Role In Alzheimers Disease.
Funder
National Health and Medical Research Council
Funding Amount
$553,236.00
Summary
Currently there are limited therapeutic treatments and no cure for Alzheimer's disease (AD). The key protein causing AD is called Abeta. Abeta peptides form dityrosine cross-linked dimers (when 2 peptides join together) and this is thought to be responsible for killing brain cells in AD. Therefore, this proposal will determine the role of Abeta dimers in relation to killing brain cells and the progression of AD through analysis of their biological and biochemical properties.
The Effect Of Metals On Neurofibrillary Tangle Formation
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
The majority of studies into Alzheimer's disease (AD) have focussed on two brain lesions- the plaque and neurofibrillary tangle (NFT), which are believed to have a causative role in AD. Our lab has made several seminal discoveries about the role that metals play in the development of plaques. We are now extending this work to evaluate the role of metals in NFT formation. These studies will provide insight into the formation and possible treatments for this primary brain lesion in AD.
An Analysis Of A Model Of Movement Disorder Lacking D1R Positive Neurons.
Funder
National Health and Medical Research Council
Funding Amount
$346,446.00
Summary
The experiments outlined in this project proposal are aimed at further characterizing a genetically engineered mouse the generation of which was originally funded by the Australian NH and MRC. The mutant mouse suffers from the loss of brain cells in a part of the brain called the striatum. The mouse model will allow us to understand how damage to brain structures cause disabling human neurodegenerative diseases such as Parkinsonism and Huntington's disease. The mouse model is unique as the mice ....The experiments outlined in this project proposal are aimed at further characterizing a genetically engineered mouse the generation of which was originally funded by the Australian NH and MRC. The mutant mouse suffers from the loss of brain cells in a part of the brain called the striatum. The mouse model will allow us to understand how damage to brain structures cause disabling human neurodegenerative diseases such as Parkinsonism and Huntington's disease. The mouse model is unique as the mice suffer from the same type of movement abnormalities which afflict individuals with this spectrum of neurological illnesses. We will look at both structural changes in the brain as well as brain function as defined by the behavioural responses of the damaged brain to drug administration. The experiments also focus on the ultimate correction of the neurological deficits by transplantation of purified nerve cell progenitor cells.Read moreRead less
GENETIC FACTORS AND REGIONAL BRAIN ATROPHY IN THE DIAGNOSIS OF DEMENTIA WITH LEWY BODIES
Funder
National Health and Medical Research Council
Funding Amount
$605,151.00
Summary
The number of people with dementia is increasing in Australia as people live longer. Dementia sometimes has a genetic basis and identification of such cases has improved our understanding of the events leading to the destruction of the brain tissue. In the vast majority of people, the degenerative changes were previously thought to be as a result of Alzheimer's disease. However, our recent research, funded by the NHMRC, confirms international findings showing more than 25% of people with dementi ....The number of people with dementia is increasing in Australia as people live longer. Dementia sometimes has a genetic basis and identification of such cases has improved our understanding of the events leading to the destruction of the brain tissue. In the vast majority of people, the degenerative changes were previously thought to be as a result of Alzheimer's disease. However, our recent research, funded by the NHMRC, confirms international findings showing more than 25% of people with dementia have a different disease called Dementia with Lewy bodies or DLB. Of course identifying these patients occurs at death when the cells in the brain can be examined for Lewy bodies. We now know that the brain degeneration differs significantly in patients with this disease. However, it is still not possible to identify DLB in life with any certainty. This project aims to develop objective methods to clinically differentiate dementia patients. We will seek out families in which genetic influences may underly the disease and determine whether these factors differ from those found in other dementing illnesses. Also, our preliminary studies have observed volume loss in a particular brain region in pathologically confirmed DLB patients. We wish to do further measurements to determine if tissue loss in this region can clinically differentiate DLB patients. In addition, we will determine the reasons for the tissue loss by careful pathological studies.Read moreRead less
Deciphering The Neuroprotective Mechanism Of Parkinsons Disease-Associated Protein Kinase PINK1
Funder
National Health and Medical Research Council
Funding Amount
$547,994.00
Summary
Parkinson's disease is caused by premature death of nerve cells that control body movements. The enzyme PINK1 protects against nerve cell death by chemically modifying specific cellular proteins that maintain cell survival. We aim at identifying these proteins and investigating how PINK1-catalysed modification modulates their ability to maintain nerve cell survival. The study will benefit development of drugs that protect against nerve cell death for treatment and prevention of the disease.