Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989920
Funder
Australian Research Council
Funding Amount
$750,000.00
Summary
Microbial and Cellular Imaging and Analysis Facility. The Microbial and Cellular Imaging and Analysis Facility will rapidly establish itself as one of Australia's premier science facilities. It will provide the capacity to investigate the structure and molecular dynamics of viruses and microbial, human, animal and plant cells with unprecedented high resolution in both pure and applied research settings, guided by Australia's leading experts in many research strengths. This facility addresses a c ....Microbial and Cellular Imaging and Analysis Facility. The Microbial and Cellular Imaging and Analysis Facility will rapidly establish itself as one of Australia's premier science facilities. It will provide the capacity to investigate the structure and molecular dynamics of viruses and microbial, human, animal and plant cells with unprecedented high resolution in both pure and applied research settings, guided by Australia's leading experts in many research strengths. This facility addresses a current unmet need for scientists in this country and will provide cutting-edge technologies to Australian researchers so they can better detect, understand, and treat human, animal and plant diseases and the environmental impact of climate change.Read moreRead less
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Epigenetic Regulation By PKC-theta In Human Breast Cancer Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$818,132.00
Summary
Treating women with advanced breast cancer is difficult, and new drugs are needed to kill the cancer stem cells that cause recurrence. We think that a newly discovered protein, PKC-?, plays an important role in recurring breast cancer and can be targeted using novel ‘epigenetic’ drugs. Here, we will use cutting-edge DNA techniques to learn how this protein controls how cancer cells grow and produce the necessary data to show that targeting this protein is likely to be effective in real patients.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Governance and economic incentives for reducing the contribution of tropical deforestation to climate change. The project will contribute toward global efforts to reduce global greenhouse gas emissions, thus mitigating the potential economic and environmental impacts of future climate change on Australia. Australia's neighbours will benefit from the project by putting them in a better position to gain financial transfers for foregone benefits of deforestation, and by insights on better systems o ....Governance and economic incentives for reducing the contribution of tropical deforestation to climate change. The project will contribute toward global efforts to reduce global greenhouse gas emissions, thus mitigating the potential economic and environmental impacts of future climate change on Australia. Australia's neighbours will benefit from the project by putting them in a better position to gain financial transfers for foregone benefits of deforestation, and by insights on better systems of governance. The positive effects enjoyed by neighbouring countries are likely to translate into improved relations with Australia. At the level of international negotiations, the research will support Australia's ambitions for a meaningful post-Kyoto climate change agreement.Read moreRead less