Intracellular Trafficking Of Copper And Platinum-based Chemotherapuetics
Funder
National Health and Medical Research Council
Funding Amount
$268,328.00
Summary
Platinum-based anti cancer drugs such as Cisplatin are effective against a number of cancers of the head, colon, lungs and ovaries. Tumour resistance to these drugs has been closely associated with changes in genes that control the movement of copper in and out of cells. We hypothesize that the same genes regulate distribution of both copper and Cisplatin. By investigating these pathways, we aim to find ways to predict and prevent tumour resistance to this important anti cancer treatment.
Molecular And Cellular Studies Of The Copper-transporting ATPases Affected In Menkes And Wilson Diseases
Funder
National Health and Medical Research Council
Funding Amount
$558,300.00
Summary
Copper is an element that is essential for life but is highly toxic in excess. Because of this, the regulation of copper uptake, distribution in the body and excretion of excess is a very tightly regulated process. Until recently little was known about the molecular basis of this process. Two genetic disorders that show these two aspects of copper are Menkes disease (deficiency) and Wilson disease (toxicity). Both diseases are caused by mutations in similar copper pumping proteins. Our research ....Copper is an element that is essential for life but is highly toxic in excess. Because of this, the regulation of copper uptake, distribution in the body and excretion of excess is a very tightly regulated process. Until recently little was known about the molecular basis of this process. Two genetic disorders that show these two aspects of copper are Menkes disease (deficiency) and Wilson disease (toxicity). Both diseases are caused by mutations in similar copper pumping proteins. Our research is trying to establish the molecular mechanisms used in the body to control copper metabolism. We made a major breakthrough in 1993 with the isolation of the gene affected in Menkes disease, and we continue to be one of the leading groups in the world in studying the molecular mechanisms that handle copper, and the importance of these mechanisms in health and disease. Research into the biology of copper has become much more important following the recent discoveries of the involvement of the metal in such important neurodegenerative conditions such as Alzheimer's, Mad Cow, and Parkinson's diseases. Health effects from the lack of copper may be widespread also, copper deficiency is suspected to contribute to some common diseases, such as cardiovascular problems and osteoporosis. Our research is providing information about copper transport mechanisms that are necessary for the understanding of, and may lead to better treatment and diagnosis of common and important diseases. In this grant we propose to continue our studies into the molecular signals that control the copper pumps, that make the regulation of copper metabolism possible. We also will use various test systems for studying the effect of mutations on the activity of these proteins and relate these effects to the type of disease produced in patients.Read moreRead less
Copper is an essential trace element with the potential for toxicity. Copper deficiency can be fatal to developing animals due to the multiple organ abnormalities caused by the reduced activity of important copper containing enzymes. Dietary copper deficiency can cause iron unresponsive anaemia in children and may contribute to heart disease and connective tissue defects in adults. A variant form of a copper containing protein is thought to contribute to Alzheimer's disease and the affected prot ....Copper is an essential trace element with the potential for toxicity. Copper deficiency can be fatal to developing animals due to the multiple organ abnormalities caused by the reduced activity of important copper containing enzymes. Dietary copper deficiency can cause iron unresponsive anaemia in children and may contribute to heart disease and connective tissue defects in adults. A variant form of a copper containing protein is thought to contribute to Alzheimer's disease and the affected protein in mad cow disease may normally play a role in copper biology of the brain. Given the importance of copper for normal health and the potential for toxicity, the levels of copper in the body are tightly regulated. There are two main sites for this regulation: the uptake of dietary copper across the intestine and the excretion of excess copper into the bile. This proposal addresses the molecular control of copper uptake in the intestine. Much of our understanding about the regulation of the uptake of copper from dietary sources was obtained prior to the era of modern molecular biology. Prof. Mercer's laboratory has recently made significant discoveries into the molecular basis of copper metabolism in human cells. Based on these findings and finding of others about copper metabolism in yeast, we have proposed a model incorporating these newly described molecules to explain how the body might regulate the uptake of copper in the intestine. We propose to investigate this model using cell culture models of the intestine and in mouse models. These studies will extend our knowledge of copper biology and may provide insight for potential treatments of copper related disorders.Read moreRead less
Copper-ionophores As A Treatment For Prostate Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$314,154.00
Summary
The overarching aim of this project is to evaluate a potential therapy for prostate cancer, which targets a distinct characteristic of the disease 'elevated copper'. Our copper-based drugs in the laboratory selectively destroy cancerous prostate cells without harming normal cells. We will verify whether these drugs work in the body where the environment is more complex. Proof of this principle will open up a new area of research and provide a novel therapeutic approach for prostate cancer.
Neurodegeneration In The Ageing Brain: How The Pathways Leading To Aggregated Protein Cause Disease
Funder
National Health and Medical Research Council
Funding Amount
$12,322,838.00
Summary
The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program ha ....The team consists of eight highly experienced research scientists who are dedicated to solving the question of how the brain degenerates in the elderly when associated with the accumulation of certain proteins: e.g. A_ amyloid (Alzheimer�s disease) and PrP (Creutzfeldt-Jakob disease). Understanding the molecular pathways leading to the degeneration (loss of neuronal synapses) will permit the development of rational diagnostic and therapeutic interventions. Over the past five years the program has identified several diagnostic and therapeutic avenues which are now being developed by the Pharmaceutical and Biotechnology industries. Much more research is still required for maximizing the chances of success using these approaches.Read moreRead less
The Prevalence And Trajectory Of Kidney Disease In Urban Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$94,515.00
Summary
The Study of Environment and Aboriginal Resilience on Child Health is a major NHMRC funded project looking at the health and illness of urban Aboriginal children in Australia. By working together with Aboriginal Community Controlled Health Services across urban and large regional centres in NSW the study team hope to better understand the causes of common diseases such as kidney and heart disease, and whether these first begin in childhood.
Computational Modelling To Understand Early-stage Neurodegeneration
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Rather than attempting to reverse neurodegeneration, therapeutic strategies must target the earliest possible stages of disease, when treatments have the potential to prevent or slow down pathological progression. The proposed project will employ computational modelling using functional MRI to deliver highly efficient and sensitive markers of Familial Alzheimer’s disease and Huntington’s disease progression to inform when in the progression of disease clinical trials should take place.