We will investigate how the master control gene, Kruppel-like factor 1, orchestrates production of red blood cells. We will use genetic and cell biology approaches to determine exactly how this factor interprets the genome blueprint in a cell specific manner. We will also determine how mutations in KLF1 cause human diseases such as congenital dyserythropoietic anemia and hereditary persistence of fetal haemoglobin. This has implications for reactivation of HbF in adults with sickle cell disease.
The Role Of Soluble Transferrin Receptor In The Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$539,607.00
Summary
Iron is both essential for health and toxic in excess so the body very tightly regulates how much iron is absorbed from the diet. One of the most important regulators of dietary iron absorption is the iron demands of developing red blood cells. In this project we will investigate how developing red blood cells signal changes in iron absorption. An understanding of this process will be of great benefit in the analysis and treatment of important blood diseases and disorders of iron metabolism.
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.
Identification And Evaluation Of Novel Epigenetic Targets For The Treatment Of ? Haemoglobin Disorders
Funder
National Health and Medical Research Council
Funding Amount
$740,809.00
Summary
Symptoms of ?-haemoglobin disorders appear after birth, when fetal haemoglobin (HbF) is replaced by aberrant adult haemoglobin (HbA). Interestingly, the persistent expression of HbF in patients reduces disease severity. This observation has created much interest in understanding the fetal to adult transition, since reversing it can benefit patients. Epigenetics plays a central role to this mechanism. Identifying components of this switch will form the basis of next generation therapies.
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorde ....Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorders.Read moreRead less
Development Of Novel Gene Therapy Vectors For Thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$287,307.00
Summary
Thalassaemia, is a common inherited disorder affecting haemoglobin synthesis. Synthesis of ?/?-globin chain is balanced during normal red blood cell production. Any disruption in the ratio of ?/?-globin chain results in anaemia. In this study, we will explore gene therapy strategies to restore balanced ?:? globin expression and ultimately improve the severely anaemic phenotype in ?-thalassaemia patients.
Thalassaemia is the most common blood disorder worldwide. In severe cases, life-long blood transfusions are needed to survive but complications including iron overload and bone disease can occur. Deferasirox, a drug used to treat iron overload has been linked to kidney stones and bone loss in these patients through increased loss of calcium in the urine. The purpose of this study is to investigate whether bone loss can be reversed by using a diuretic or an alternative iron chelator.
Thalassaemia, is a common inherited disorder affecting haemoglobin synthesis. Synthesis of ?/?-globin chain is balanced during normal red blood cell production. Any disruption in the ratio of ?/?-globin chain results in anaemia. In this study, we will explore gene therapy strategies to restore balanced ?:? globin expression and ultimately improve the severely anaemic phenotype in ?-thalassaemia patients.
A Novel Genetic Element Controlling Adult Hemoglobin Production
Funder
National Health and Medical Research Council
Funding Amount
$493,907.00
Summary
Disorders of the blood protein hemoglobin are the commonest genetic diseases worldwide, and include thalassemia and sickle cell disease. In this proposal we study two novel mouse lines that exhibit thalassemia, but lack any of the known genetic mutations that cause this disease. These mice afford us the opportunity to make unique observations into how hemoglobin is produced, and thereby provide a platform for new therapeutic approaches in these devastating diseases of the blood.