Iron Overload Mechanisms In Dyserythropoietic Anaemias And Therapeutic Targets At The ERFE Gene Locus
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Iron overload causes organ dysfunction and morbidity for people who have red blood cell disorders such as thalassemia, or chronic transfusion requirements due to cancer or bone marrow failure. The manner in which a principal controlling compound, erythroferrone, influences iron metabolism is undefined. Our project will use molecular approaches to determine how the erythroferrone gene is involved in causing iron overload in red cell disorders and potentially open better management pathways.
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.
Mechanisms Of Intestinal Iron Absorption And Consequences Of Iron Supplementation During The Perinatal Period
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Iron intake is particularly high during pregnancy and in the newborn to meet the requirements of the growing fetus and neonate. While it is widely recommended that women take iron supplements at this time, too much iron may adversely affect pregnancy outcome. The aim of this study is to understand the factors controlling iron intake in the perinatal and the consequences of excess iron. This will provide the physiological information required to make rational decisions about iron supplementation.
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
The Mechanism Of Intestinal Haem Iron Absorption And Characterization Of A Novel Haem-binding Protein
Funder
National Health and Medical Research Council
Funding Amount
$537,773.00
Summary
Iron is essential for normal health as many important proteins in the body require iron to function properly (e.g. haemoglobin). However, too much iron can be toxic, so the body must keep its iron content within defined limits. The amount of iron in the body is determined at the point of absorption from the diet in the small intestine. If too little iron is absorbed, then anaemia can result. If too much iron is absorbed, as is the case in the common disease haemochromatosis (with approximately 1 ....Iron is essential for normal health as many important proteins in the body require iron to function properly (e.g. haemoglobin). However, too much iron can be toxic, so the body must keep its iron content within defined limits. The amount of iron in the body is determined at the point of absorption from the diet in the small intestine. If too little iron is absorbed, then anaemia can result. If too much iron is absorbed, as is the case in the common disease haemochromatosis (with approximately 1 in 200 Australians at risk) then the body becomes iron loaded and various organs, particularly the liver, can become damaged. An understanding of how iron is absorbed will place us in a much better position to treat diseases such as this. Iron is present in the diet in two forms - inorganic iron and haem iron. Inorganic iron is the main form of iron in foods of plant origin while most haem iron comes from meat. In a typical diet 80-90% of the iron is inorganic iron and only 10-20% is haem. Despite this, 30-50% of the iron taken into the body comes from haem, so haem iron absorption is particularly efficient. While we have learned a great deal about the mechanims by which inorganic iron is absorbed in recent years, we know very little about the absorption of haem iron, so that is the focus of this project. We will study the pathway by which haem enters the body, how this process is regulated, and the characteristics of haem binding to the cells lining the small intestine. These cells are responsible for the uptake of all nutrients from the diet. In particular, we will examine the biology of a recently identified protein known as HCP1. Preliminary evidence suggests that HCP1 could be the main protein enabling haem to be taken up by intestinal cells. These studies will enhance our knowledge of an important nutritional pathway and improve our capacity to treat diseases such as haemochromatosis where iron absorption is defective.Read moreRead less
The Role Of Transferrin Receptor, Divalent Metal Transporter, Ferroportin And Hemochromatosis Protein In Iron Absorption
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
Within Australia 1 in 300 people of Caucasian origin have a genetic defect which makes them absorb more iron from the diet than they need. Excess iron is a major problem because it damages cells and this is most obvious in the pancreas where the cells make insulin are destroyed and diabetes mellitus develop. In the liver cirrhosis and cancer often occur. Iron also accumulates in other tissues such as the heart and joints resulting in damage to these organs. The genetic defect has recently been i ....Within Australia 1 in 300 people of Caucasian origin have a genetic defect which makes them absorb more iron from the diet than they need. Excess iron is a major problem because it damages cells and this is most obvious in the pancreas where the cells make insulin are destroyed and diabetes mellitus develop. In the liver cirrhosis and cancer often occur. Iron also accumulates in other tissues such as the heart and joints resulting in damage to these organs. The genetic defect has recently been identified but how the defective protein causes the cells of the intestine to absorb more iron into the body than is needed remains unknown. This has led to the idea that the normal protein is responsible for controlling the amount of iron absorbed. Recent studies have shown a link between this protein and another called transferrin receptor. These two molecules are thought to co-operate in determining how much iron will be absorbed. Once this is determined other molecules called iron transporters are produced and these are responsible for moving the iron from the intestine into the blood. When not much iron is required only a small number of transporters are made and when more iron is required then many more are produced. How these transporters program the level of iron absorption is unknown but the process probably involves the transferrin receptor and the hemochromatosis protein. This project will investigate the function of the molecules that determine the programe for how much iron is to be absorbed, and secondly how this is linked to the production and movement of the transproters that co-ordinate this function.Read moreRead less
Iron is essential in the diet but it is also toxic when present in excess, so both iron deficiency and iron overload can have significant clinical consequences. I will investigate the basic mechanisms by which the body acquires iron and how iron can lead to toxicity. The goal of these studies is to provide more effective iron supplements and to improve diagnosis and treatment of iron-related diseases. Iron metabolism in pregnancy, infants and respiratory diseases will be a particular focus.