Using Nanotechnology To Improve The Therapeutic Efficacy Of Iron Chelators
Funder
National Health and Medical Research Council
Funding Amount
$692,769.00
Summary
Iron loading disorders (such as thalassaemia) represent an important class of human disease. As part of the treatment for these diseases, the iron needs to be removed and this is often done using iron-binding drugs known as iron chelators. Current chelators are not ideal due to side effects or onerous delivery methods. The goal of this project is to use nanotechnology to develop more effective ways of delivering chelators to improve their effectiveness and reduce toxicity.
The lung in people with the genetic disorder cystic fibrosis (CF) contains increase amounts of iron, which promotes bacterial infection. In this research project we are using mouse models of CF and airway cells obtained from people with CF to investigate the underlying mechanism of abnormal iron regulation. We are also examining the therapeutic potential of compounds that interfere with the ability of bacteria to obtain iron to see whether this can overcome antibiotic resistance.
Development Of Iron Complexes For The Treatment Of FriedreichÍs Ataxia & The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$616,143.00
Summary
Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal c ....Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal could lead to novel therapies for FARead moreRead less
Beige fat is a recently described kind of fat which instead of storing fat and contributing to obesity burns energy and burns glucose. It helps to combat obesity and diabetes. If it could be increased and switched on, it would help to treat obesity and diabetes. This grant will study a new pathway to try to increase the amount of beige fat and to increase its activity.
Investigating The Cellular Response To Iron-Depletion: The Trilogy Of ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$552,572.00
Summary
Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for t ....Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.Read moreRead less
Lipophilic Iron Chelators As Potential Therapeutic Agents In Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$616,537.00
Summary
The impaired coordination and tremors experienced by the 64,000 Australians with Parkinson’s disease make managing life at work and home difficult. With 240,000 Australians projected to be living with Parkinson’s disease by 2033, the discovery of agents that slow or stop disease progression is urgent. Iron in the brain has been implicated in Parkinson’s disease. In this project, the performance of new low toxicity agents in altering brain iron distribution will be studied as potential drugs for ....The impaired coordination and tremors experienced by the 64,000 Australians with Parkinson’s disease make managing life at work and home difficult. With 240,000 Australians projected to be living with Parkinson’s disease by 2033, the discovery of agents that slow or stop disease progression is urgent. Iron in the brain has been implicated in Parkinson’s disease. In this project, the performance of new low toxicity agents in altering brain iron distribution will be studied as potential drugs for Parkinson’s disease.Read moreRead less
Mechanisms Of Intestinal And Systemic Iron Homeostasis In Early Infancy
Funder
National Health and Medical Research Council
Funding Amount
$485,835.00
Summary
Iron is essential trace element for normal health. Iron requirements are particularly high during early postnatal life to meet the needs of the growing infant. To accommodate these needs, intestinal iron absorption is extremely high at this time. We have previously shown that the iron absorption mechanism during suckling differs from that in adults and this project explores that mechanism in more detail. These studies have important implications for infant nutrition and dietary supplementation.
Role Of Non-transferrin Bound Iron In Iron Overload Disease
Funder
National Health and Medical Research Council
Funding Amount
$669,504.00
Summary
Plasma non-transferrin bound iron (NTBI) levels are elevated in iron overload disorders. Excess NTBI has serious health consequences as it is toxic and may induce cellular dysfunction and injury. We will investigate the molecular mechanisms by which NTBI transport is regulated, the contribution of NTBI to the development of iron overload and its impact on oxidative-mediated liver and heart injury in iron overload conditions associated with Hereditary Haemochromatosis and thalassaemia.
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
Defining Iron And Haem-induced Pro-carcinogenic Pathways Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$566,277.00
Summary
Colorectal cancer is very common in Western society. Population studies have reported that high consumption iron-containing foods and red meat, the latter being a source of both haem and iron, are risk factors for colorectal cancer. This study will identify the levels of dietary haem and iron that promote colorectal cancer development. Also, it will determine the mechanisms and relative contribution of iron and haem to pro-carcinogenic pathways that result in colorectal cancer.