Dissecting The TMPRSS6 Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia
The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has l ....The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has led to fundamental observations of iron regulation and homeostasis and the development of guidelines for the management of, and screening for, haemochromatosis, recognized as the most common inherited disorder of Caucasian populations. The proposed research encompasses molecular studies aimed at deciphering the mechanisms of iron absorption and transport; how these processes are regulated; and clinical studies on patients diagnosed with haemochromatosis. The findings are particularly pertinent to the diagnosis, management and prevention of clinical haemochromatosis.Read moreRead less
Non-HFE Haemochromatosis In Australia: Natural History And Molecular Characterisation
Funder
National Health and Medical Research Council
Funding Amount
$179,948.00
Summary
Hereditary haemochromatosis (HH) is a disorder characterised by excessive iron absorption and build up of iron in body organs such as the liver. The excess iron can be toxic and cause disease. Most HH is caused by mutations in the HFE gene. Other forms are caused by mutations in other genes. This project will characterise a new form of HH that is unrelated to any of the previously known genes. The project aims to find the gene for this new condition by genetic analysis in a large family.
EXAMINING THE RELATIONSHIP BETWEEN MATRIPTASE-2 AND HEMOJUVELIN, TWO ESSENTIAL REGULATORS OF IRON HOMEOSTASIS
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
The control of iron levels is important in health and well being. Too little can lead to iron deficiency and anaemia, conversly too much can lead to haemochromatosis and tissue damage. We will examine the role of two proteins, matriptase-2 and hemojuvelin that when mutated cause iron deficiency or iron overload respectively. We will study how these proteins interact and work in opposite directions to control iron levels. The results will help to develop new therapeutics for iron disorders.
Preconception Predictors Of Health, Behaviour And Emotional Adjustment At Seven Years
Funder
National Health and Medical Research Council
Funding Amount
$1,170,830.00
Summary
An understanding of the importance of a healthy start to life has underpinned major health policies including Australia’s National Agenda for Early Childhood. The capacity of parents to provide that healthy start has received little study. The present project investigates the extent to which parental lifestyle, social and emotional adjustment prior to conception predictor emotional problems, disruptive behaviour and health in their children at seven years.
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Delineating The Relationship Between Iron And Peroxisomal Disorders: The Role Of The Peroxisomal Enzyme GNPAT In Iron-Overload Disorders
Funder
National Health and Medical Research Council
Funding Amount
$700,767.00
Summary
Hereditary haemochromatosis is one of the most common genetic disorders in humans, affecting 1 in 200 Australians. We have identified a change in a peroxisomal gene which may affect iron levels in humans. The prevalence of this gene change in Australian haemochromatosis patients will be examined followed by a systematic analysis of how this protein controls iron levels in the body. Our goal is to identify and diagnose genetic changes which influence iron loading in haemochromatosis patients.
A Practice Change For Patients With Severe Chronic, Clinically Unexplained Gastrointestinal Symptoms: A Randomised, Controlled Intervention To Assess Efficacy And Cost-effectiveness
Funder
National Health and Medical Research Council
Funding Amount
$1,276,080.00
Summary
Unexplained chronic gastrointestinal symptoms are extremely common and costly to the health system. Currently patients are managed in the hospital setting with the 'typical' face-to-face office-based model which sees the clinician spending valuable time gathering information and often treatments (e.g. allied health) delivered in a non-standard way. This project will evaluate the effectiveness of a new standard best-practice clinical model with a structured technology enabled management approach.
Industrial Transformation Research Hubs - Grant ID: IH230100010
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Research Hub for Smart Process Design and Control . ARC Research Hub for Smart Process Design and Control aims to develop and apply advanced computational technologies to model and optimise complex multiphase processes by integrating the novel multiscale and AI modelling approaches. The outcomes include theories, computer models and simulation techniques, advanced knowledge about process modelling and optimisation, innovative technologies and processes for low carbon operations, and tens of ....ARC Research Hub for Smart Process Design and Control . ARC Research Hub for Smart Process Design and Control aims to develop and apply advanced computational technologies to model and optimise complex multiphase processes by integrating the novel multiscale and AI modelling approaches. The outcomes include theories, computer models and simulation techniques, advanced knowledge about process modelling and optimisation, innovative technologies and processes for low carbon operations, and tens of postdoc and PhD students through academic, industrial and international collaboration. Their application will significantly improve energy/process efficiency and reduce CO2 emission. The Hub will generate a significant impact on the mineral and metallurgical industries which are important to Australia.Read moreRead less
ARC Centre of Excellence for Carbon Science and Innovation. ARC Centre of Excellence for Carbon Science and Innovation. This Centre aims to develop carbon-based catalysts for clean energy, CO2 capture, and green chemistry to reduce emissions. The Centre expects to use pioneering data-guided atomic-precision synthesis and multiscale analysis to transform fundamental science of carbon materials. Expected outcomes of this Centre will benefit new technologies for energy, environmental, and green che ....ARC Centre of Excellence for Carbon Science and Innovation. ARC Centre of Excellence for Carbon Science and Innovation. This Centre aims to develop carbon-based catalysts for clean energy, CO2 capture, and green chemistry to reduce emissions. The Centre expects to use pioneering data-guided atomic-precision synthesis and multiscale analysis to transform fundamental science of carbon materials. Expected outcomes of this Centre will benefit new technologies for energy, environmental, and green chemical industries by utilising abundant sunlight, seawater, and waste feedstocks. This should provide significant benefits, through industry collaborations, our new world-leading capacity will train a next generation of game changers to empower emerging carbon industries to solve grand socio-economic challenges, ultimately meeting zero-carbon emissions targets.Read moreRead less