Characterising Protein And Membrane Changes In Age-related Cataract Lenses.
Funder
National Health and Medical Research Council
Funding Amount
$441,624.00
Summary
Cataract is the major cause of blindness worldwide. At present the only treatment for cataract, is surgery. This, however, is associated with complications (e.g. posterior capsule opacification), is expensive (a major component of the Health budget) and cannot keep pace with the incidence of cataract in developing nations. In addition, due to the greying of the community , this problem will be of increasing importance in the future. For prevention, we need to understand why cataract develops.
The Role Of Differentially Methylated Genes In The Initiation And Progression Of Colorectal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$361,527.00
Summary
Most colorectal cancers develop from polyps in the lining of the bowel. The bulk of cancers develop from adenomatous polyps, but we have found that a second type of polyp called a hyperplatic polyp can also be associated with the development of cancer. During our studies of these polyps we found that a particular gene was inactivated in all of these polyps. We have called this gene HPP1. HPP1 was also found to be inactivated in adenomatous polyps and about 50% of colorectal cancers, indicating t ....Most colorectal cancers develop from polyps in the lining of the bowel. The bulk of cancers develop from adenomatous polyps, but we have found that a second type of polyp called a hyperplatic polyp can also be associated with the development of cancer. During our studies of these polyps we found that a particular gene was inactivated in all of these polyps. We have called this gene HPP1. HPP1 was also found to be inactivated in adenomatous polyps and about 50% of colorectal cancers, indicating that it may be an important player in the early stages of colorectal cancer and hence may allow opportunity for prevetive intervention. This grant proposal will investigate the function of HPP1 in the genesis of colorectal polyps and cancers.Read moreRead less
Characterisation Of Precursor Lesions In Colorectal Cancers With DNA Instability
Funder
National Health and Medical Research Council
Funding Amount
$60,190.00
Summary
It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely differ ....It is now generally accepted that most colorectal cancers arise from previously benign lesions in the mucosal lining of the large bowel. These lesions are called adenomatous polyps. They have been extensively studied as have the cancers which evolve from them with regard to the type of cancer causing genetic changes they bear. Recently, it has been found that colorectal cancer is not a single disease in that there exists a subgroup comprising 15% of colorectal cancers which is an entirely different type wwith respect to genetic changes and biological behaviour. This subgroup contains cancers with a high level of microsatellite instability (MSI-high) and the cancers which comprise this group show none of the common genetic changes which can be demonstrated in both adenomatous polyps and the 85% of colon cancers which develop from them. The MSI-high colorectal cancers do however share some striking similarities to a type of polyp (hyperplastic) which has until quite recently been considered of little consequence. Our research group and others have shown an association with colorectal cancer in those patients in whom hyperplastic polyps are unusually large or numerous, especially if present in the right side of the large bowel, where the bulk of MSI-high colorectal cancers arise. The current proposal will investigate the hyperplastic polyp as a precursor lesion in the genesis of MSI-high cancers.Read moreRead less
Amyloid Abeta In The Natural History Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$220,475.00
Summary
This grant is the continuation of a large series of experiments designed to uncover the basic causes of Alzheimer's disease. The focus is on closing some of the gaps in our knowledge of the natural history of Alzheimer's disease in relation to the deposition of the Abeta amyloid protein in the brain, which we believe plays a central role in the degeneration of nerve cells in this condition. The main questions we are tackling include: the feasibility of using assays of Abeta in the blood as a bio ....This grant is the continuation of a large series of experiments designed to uncover the basic causes of Alzheimer's disease. The focus is on closing some of the gaps in our knowledge of the natural history of Alzheimer's disease in relation to the deposition of the Abeta amyloid protein in the brain, which we believe plays a central role in the degeneration of nerve cells in this condition. The main questions we are tackling include: the feasibility of using assays of Abeta in the blood as a biological marker of Alzheimer's disease; whether better transgenic mouse models of Alzheimer's disease are required; whether the soluble forms of Abeta amyloid are the major species which cause neurotoxicity (in contrast to the insoluble forms which constitute the bulk of this protein in the Alzheimer's disease brain); and whether the intracellular or extracellular pathways of Abeta aggregation and toxicity are the key to understanding this disease. Increasing evidence suggests that the clearance of soluble forms of the Abeta protein from the brain may be a major therapeutic strategy. We therefore require further investigations of how these soluble forms of Abeta are generated in nerve cells, and how these forms exist in equilibrium with soluble and insoluble pools in the brain, cerebrospinal fluid, blood and other tissues of the body.Read moreRead less
Regulation And Substrate Identification Of Parkinsons Disease Causative Leucine-rich Repeat Kinase 2 (LRRK2)
Funder
National Health and Medical Research Council
Funding Amount
$699,456.00
Summary
Parkinson's disease afflicts 100,000 Australians. Mutations in the recently identified enzyme Leucine-rich Repeat Kinase-2 are a common cause of Parkinson's disease. This project will use biochemical methods to understand how this brain enzyme causes disease by investigating its enzymology, modes of regulation, and target substrates that it modifies by addition of phosphate groups. Characterization of this enzyme will facilitate design of inhibitors to slow the course of Parkinson's disease.
Effect Of Aging And Mitochondrial Dysfunction On The Optic Nerve Response To Pressure-induced Oxidative Stress
Funder
National Health and Medical Research Council
Funding Amount
$415,554.00
Summary
The risk of glaucoma, a potentially blinding disease of the optic nerve, increases exponentially with age, but the cellular mechanisms responsible are not known. We hypothesise that age-related changes in mitochondria, the energy producing part of the cell, render nerve cells prone to damage. This project will determine whether aging and mitochondrial impairment increase nerve damage and whether dietary moodifications that preserve mitochondria during aging, protect the optic nerve from damage
Astrocyte-Neuron Communication: Unravelling The Role Of Astrocytes In The Modulation Of Neuronal Circuits
Funder
National Health and Medical Research Council
Funding Amount
$403,064.00
Summary
Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neur ....Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neurodegenerative states (e.g. Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Many of these diseases are associated with a pathological astrocyte process known as 'reactivity'. This process remains enigmatic, resulting in so-called reactive gliosis, a reaction characterized by changes in gene expression, cell enlargement and changes in cell shape, and, in some cases, cell division. Most of the research on astrocyte reactivity has focused on the impairment of astrocyte metabolic activities. Comparatively little is known about the effect of reactive gliosis on so called 'newer' astrocyte roles such as their ability to interact with each other and nearby neurons using exocytosis of gliotransmitters (GTs: glutamate and ATP) and neurotrophic factors (NTFs: glial and brain derived neurotrophic factors). This project will both further investigate the normal mechanisms of astrocyte-neuron communication, and examine the effects of astrocyte reactivity on these mechanisms. The aim is to identify possible therapeutic targets to ameliorate the detrimental affects of neurodegeneration.Read moreRead less
Age-related Changes In Vision And Cognitive Performance: Are There Cognitive Benefits From Cataract Surgery?
Funder
National Health and Medical Research Council
Funding Amount
$101,074.00
Summary
It is possible that some of the confusion and memory loss experienced by older people is due to perceptual errors resulting from poor vision. If this is the case, then treating visual impairment may improve everyday cognitive functioning in some older people. This study aims to find out if the improvement in vision experienced after cataract surgery leads to improvement in memory and cognitive processing among older persons. The study will follow a group of adults aged 70 and older who are about ....It is possible that some of the confusion and memory loss experienced by older people is due to perceptual errors resulting from poor vision. If this is the case, then treating visual impairment may improve everyday cognitive functioning in some older people. This study aims to find out if the improvement in vision experienced after cataract surgery leads to improvement in memory and cognitive processing among older persons. The study will follow a group of adults aged 70 and older who are about to undergo cataract surgery and test them on measures of cognitive performance before surgery, and 3 and 12 months after surgery. Another group of older adults with cataracts who have not yet had surgery and a non-cataract group will also be studied over the 12 month period. The hypothesis of the study is that the group who have had cataract surgery will show greater improvement on the measures of memory and cognitive processing over the follow-up period than the other two groups. The design of the study will allow us to determine whether improvement is due to either; a) simply being able to see the tests better, b) improvement in mood and social participation as a result of cataract surgery; c) changes in the brain that occur from increased sensory stimulation; or d) a combination of these factors.Read moreRead less