How Does Fra-1 Regulate The Invasive Properties Of Tumour Cells?
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Most cancer deaths occur when tumours spread and destroy vital body functions. The invasion of tumour cells into surrounding tissue is a critical step during the spread of cancer. This project aims to unravel the molecular mechanisms that control the ability of tumour cells to invade into surrounding tissue and subsequently spread to other sites in the body. We expect to identify potential targets to better diagnose and treat the spread of cancer.
Interleukin-6 -gp130 Signaling And Actions In The CNS
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
Interleukin-6 (IL-6) is a member of a family of cytokine proteins that may be causative factors in many neurological disorders where they are involved in diverse processes including inflammation, neuronal injury and repair. In this project we will study how IL-6 affects the brain to bring about these outcomes. The results of this work will advance our understanding of how members of this cytokine family function and how they contribute to neurological disease.
The Leucine Rich Repeat Kinase 1 And 2 Genes Are Modulators Of Alternative Splicing - Implication For Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$583,809.00
Summary
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two common causes of dementia and neurodegeneration. Through positional cloning, we have identified the leucine rich repeat kinase (LRRK1) 1 gene as a modulator of alternative splicing. We have subsequently shown that its homologue, LRRK2 has a similar biological activity. We propose to study the the genetic and biochemical role of LRRK1 and LRRK2 in neurodegeneration in terms of its effect in splicing.
Molecular Pathology Of Collagen VI-related Muscular Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$574,500.00
Summary
The inherited muscular dystrophies, characterised by progressive muscle weakness and wasting, are a significant cause of physical disability. Muscle cells are anchored into the surrounding tissue by a chain of interacting proteins. Proteins inside the cell link to cell surface proteins, which in turn link to extracellular matrix proteins. If any one of the links is broken by a mutation, the connection is lost and muscle disease results. Most studies to date have focused on the role of intracellu ....The inherited muscular dystrophies, characterised by progressive muscle weakness and wasting, are a significant cause of physical disability. Muscle cells are anchored into the surrounding tissue by a chain of interacting proteins. Proteins inside the cell link to cell surface proteins, which in turn link to extracellular matrix proteins. If any one of the links is broken by a mutation, the connection is lost and muscle disease results. Most studies to date have focused on the role of intracellular and cell surface proteins, and relatively little attention has been paid to the extracellular matrix proteins. Mutations in the extracellular matrix protein collagen VI have been found in patients with Bethlem myopathy and Ullrich muscular dystrophy. These mutations tell us that collagen VI plays a critical role in muscle but we don't know how the mutations break the link between the cell and the matrix or why they cause a muscle disease. We will look for collagen VI mutations in our group of new Bethlem myopathy and Ullrich patients, and perform detailed studies on the effect of the mutations on collagen VI production, structure and function. These studies will allow us to provide accurate diagnosis and genetic counselling for affected individuals and begin to tell us how the mutations break the cell-matrix link. Mutations in other extracellular matrix proteins that interact with collagen VI are also likely to cause muscular dystrophies. One of these proteins is biglycan. We know from studies in mice that when biglycan is missing the mice have muscular dystrophy, so it is likely that some human muscular dystrophy patients have biglycan mutations. We will look for biglycan mutations in patients with muscular dystrophies and perform detailed studies to try to understand the effect of the mutations on the biglycan protein. This application brings together two groups with complementary expertise, to further our understanding of the basis of muscular dystrophies.Read moreRead less
Epigenetics is a term that describes modification of gene expression without a change to the DNA sequence, through processes that involve chemical changes to the DNA such as DNA methylation and binding of specific proteins. It is now well established that epigenetics plays a major role in cancer development, but one of the important questions still to be resolved is the mechanism that is responsible for epigenetic changes. Our recent work has uncovered a new mechanism of epigenetic gene silencin ....Epigenetics is a term that describes modification of gene expression without a change to the DNA sequence, through processes that involve chemical changes to the DNA such as DNA methylation and binding of specific proteins. It is now well established that epigenetics plays a major role in cancer development, but one of the important questions still to be resolved is the mechanism that is responsible for epigenetic changes. Our recent work has uncovered a new mechanism of epigenetic gene silencing in cancer that can effect large chromosomal regions. We have found that both methylated and unmethylated genes can be silenced by changes to the pattern of proteins that bind to the DNA in a cancer cell. Our data also indicates that this silencing can be reversed using epigenetic drugs. This finding represents a new paradigm in epigenetic control and has major implications not only on cancer diagnostics but also cancer epigenetic therapy. In this grant we propose to further characterise and understand the mechanism involved in long range epigenetic silencing and to determine its prevalence in cancer. This proposal will shed light onto the process underlying long range epigenetic gene silencing in cancer and will provide potential novel targets for cancer detection, prognosis and therapy.Read moreRead less
Epigenetic Silencing Of Large Chromosomal Regions In Prostate Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$745,356.00
Summary
Epigenetics is a term that desribes modification of gene expression without a change to the DNA sequence through processes that involve chemical change to the DNA such as methylation. In this grant we will further characterise and understand the mechanism involved in long range epigenetic silencing and determine its prevalence in prostate cancer. This study will provide potential novel targets for prostate cancer detection, prognosis and therapy.
Neurexin And Neuroligin: A Code For Synaptic Development
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
As soon as we are born, we interpret our world through our senses, learn new information and lay down memory. These processes require molecules that connect neurons together. Mutations in genes encoding these molecules result in incorrect wiring of the brain and lead to mental disorders such as autism and schizophrenia. Using simple insect models, our project aims to unravel the fundamental mechanisms of how these molecules function in the brain and how their interaction controls behaviour.
Scleroderma or systemic sclerosis is a debilitating disease that is characterised by fibrosis of multiple organs leading to organ failure and eventually death. There is currently no cure for the disease. We are beginning to find that a newly-discovered class of molecules, called microRNAs, regulate many disease states but its role in scleroderma has not been established. We aim in this study to identify disease-related changes in microRNAs which may subsequently be used as therapeutic targets.
The Role Of Med12, A Subunit Of RNA Polymerase II Mediator, In Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$495,490.00
Summary
In a screen of zebrafish for mutations in blood cell development, we isolated a mutant called syrah. The mutation causing the blood defect was identified in a gene called med12, which encodes a component of the RNA transcription machinery in cells. To understand how this mutation causes a reduction in blood cells, we will identify the proteins that interact with the med12 protein. Understanding the pathway involved may lead to the discovery of new causes of human congenital blood diseases.
The Role Of The Thioredoxin System In Angiogenesis And Impaired Neovascularisation In Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$306,501.00
Summary
For many sufferers of heart disease who suffer from blocked coronary arteries, current treatments (e.g. bypass surgery or angioplasty) are unable to offer relief from the debilitating effects of occluded arteries. This is particularly true of patients with diabetes who have more aggressive blockages. We plan to study a newly identified mechanism to facilitate growth of new blood vessels to sites affected by vascular disease . Ultimately, this may result in new treatments for heart disease.