Blood Protein Biomarkers For Frontotemporal Lobar Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$184,305.00
Summary
This project will assess blood proteins as biomarkers for different pathogenic forms of frontotemporal dementia (FTD), one of the major neurodegenerative dementias with a very rapid disease progression (mean survival 3 years). At present, it is not possible to predict which pathological variant is present in any given patient. We plan to develop blood protein biomarker assays capable of diagnosing the pathology in vivo.
Inclusion Body Proteins And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$389,164.00
Summary
Parkinson's disease affects 1% of people aged over 50, and a related disorder, Dementia with Lewy bodies, causes dementia in elderly patients. These diseases are characterised by inclusion bodies (Lewy bodies) in a sub population of nerve cells. Multiple system atrophy, another adult-onset neurodegenerative disorder, is also characterised by inclusion bodies (glial inclusions). Inclusions may interfere with cellular function, contributing to the process of brain degeneration. The inclusion bodie ....Parkinson's disease affects 1% of people aged over 50, and a related disorder, Dementia with Lewy bodies, causes dementia in elderly patients. These diseases are characterised by inclusion bodies (Lewy bodies) in a sub population of nerve cells. Multiple system atrophy, another adult-onset neurodegenerative disorder, is also characterised by inclusion bodies (glial inclusions). Inclusions may interfere with cellular function, contributing to the process of brain degeneration. The inclusion bodies are precipitations of proteins and other cellular chemicals. In the last 10 years, in a search for the underlying cause of these neurodegenerative disorders, there has been an intensive research effort to identify the proteins precipitated in the inclusion bodies. The present project adopts a new strategy and aims to identify the precipitated proteins in the inclusion bodies in brains of people dying with Parkinson's disease, Dementia with Lewy bodies and Multiple system atrophy. We intend to isolate the Lewy bodies and the glial inclusions from fresh brain tissue of patients dying with relevant diseases. Throughout the various steps in the isolation process, the location of the inclusion bodies will be checked with a special antibody to a particular protein (alpha synuclein) which we and others have already discovered to be present in all inclusion bodies. Proteins will then be identified using electrophoresis and amino acid sequencing. With the identification of these proteins, their role in neurodegeneration in these diseases can be examined using multiple biomedical approaches. These proteins will be important candidates for developing novel diagnostic reagents, screening for gene mutations in patients, or as the target of therapeutic intervention in these diseases.Read moreRead less
Deficiency of the protein dysferlin causes muscular dystrophy, an inherited degenerative disorder of skeletal muscle. Interestingly, muscle disease due to deficiency of dysferlin does not occur until early adulthood. Affected individuals are very active with normal strength until this age and then there is rapid progression of weakness. Many patients lose the ability to walk within a few years of onset. Little is known about the functional role of dysferlin in muscle, how dysferlin deficiency re ....Deficiency of the protein dysferlin causes muscular dystrophy, an inherited degenerative disorder of skeletal muscle. Interestingly, muscle disease due to deficiency of dysferlin does not occur until early adulthood. Affected individuals are very active with normal strength until this age and then there is rapid progression of weakness. Many patients lose the ability to walk within a few years of onset. Little is known about the functional role of dysferlin in muscle, how dysferlin deficiency results in muscular dystrophy, or why dysferlin-deficient muscle is functionally normal prior to the rapid onset of symptoms. Therefore, the goal of this study is to characterize the role of dysferlin in normal and diseased skeletal muscle. We will examine the consequence of dysferlin-deficiency in patient muscle biopsy samples and patient muscle cells in culture. We will assess the role of dysferlin in the fusion and formation of new muscle cells, examine the effect of dysferlin-deficiency on muscle membrane repair, and establish how normal and mutant dysferlin is made, trafficked and degraded within muscle cells. This research will have immediate applications to the diagnosis and counselling of patients with dysferlin-related disease. In addition it will provide valuable information concerning the mechanisms of disease, essential to the development of specific and successful therapies.Read moreRead less
Preparing Australia For Genomic Medicine: A Proposal By The Australian Genomics Health Alliance
Funder
National Health and Medical Research Council
Funding Amount
$25,000,000.00
Summary
The sequencing of the human genome brings the possibility of more accurate identification of the underlying basis of many diseases. This technology has moved so rapidly, however, that clinical access has been limited. In this application, a national alliance of clinicians, researchers, health economists and policymakers will evaluate the case for clinical genomics across inherited disease and cancer, determine how best to deliver this to the patient and train a capable workforce.
Electrophysiologic Phenotyping Of Non Ischaemic Cardiomyopathy To Predict Clinical Outcome
Funder
National Health and Medical Research Council
Funding Amount
$374,676.00
Summary
Non-ischemic cardiomyopathy (NICM) is a common cause of heart failure and sudden death. Currently, the guidelines for the management are generalised and do not differentiate patients at high risk of disease progression and sudden death. This project aims to identify the electrical and structural properties of heart, to predict the clinical course in patients with NICM. Identification of high-risk patients will help allocate resources wisely and enable appropriate patient counselling.
Study Of C-KIT Mutations In Familial Gastrointestinal Stromal Tumours, Melanoma And A Novel Form Of Waardenburg Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$68,378.00
Summary
The primary aim of this research project is to study mutations in a cancer causing gene called c-KIT. We seek to identify tumour characteristics which are predictive for the presence of particular types of c-KIT mutations in melanomas and gastrointestinal stromal tumours. The detection of tumours harbouring these mutations will help in the treatment of cancer sufferers because this group of patients have been shown to respond very well to a class of drugs known as tyrosine kinase inhibitors.
SNAC2: A Randomised Trial Of Extending Sentinel Node Based Management To Women With Larger Or Multifocal Breast Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,266,430.00
Summary
SNAC2 extends the work begun in SNAC1, which recruited 1,088 women over 4 years. SNAC1 will determine if sentinel node biopsy causes less arm problems than axillary clearance. The goal of SNAC2 is to establish the risk of local recurrence and long term safety of sentinel node biopsy, especially for women with larger or multiple tumours. SNAC2 is needed to determine whether the smaller operation gives cure rates as good as axillary clearance. If it does, then it will become standard practice.
Differences Between Physiological And Pathological Cardiac Hypertrophy Offer New Strategies For Treating Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$335,473.00
Summary
The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Spec ....The heart becomes large both in athletes as well as in patients with heart disease and failure. In the first instance, the large (hypertrophied) heart has normal or even increased pumping ability (function) whereas in the patient with heart disease the function is depressed and the heart may fail. My studies are directed towards finding out what is the difference in these 2 situations and what mechanisms are responsible for making one big heart pump well and the other big heart pump poorly. Specifically my project hopes to identify the genes and proteins responsible for the differences. I have already identified one such gene and I now plan to manipulate this gene by overexpressing it in animals (transgenic mice) with heart failure. I predict that overexpression of this gene will improve heart function in models of heart failure. If the hypothesis is correct, activating genes that are activated in the athlete's heart maybe a potential tool for improving heart function, quality of life and life span in patients with heart failure.Read moreRead less