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.
Myelodysplastic Syndrome And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$562,654.00
Summary
We are interested in how myelodysplastic syndrome (MDS) affects the function of the bone marrow. We believe that changes associated with anaemia of MDS cause the bone marrow to be altered. This proposal addresses this question and explores new treatment approaches
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.
Defining The Role Of RNA Editing In Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$628,945.00
Summary
We are seeking to understand how red blood cells are produced. We have identified that a process called RNA editing may be important in the regulating the production of red blood cells.
Cytoskeletal Remodeling Of The Erythrocyte During Malaria Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$559,807.00
Summary
Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease ....Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease establishment.Read moreRead less
Cellular And Molecular Characterization Of Erythroid Enucleation
Funder
National Health and Medical Research Council
Funding Amount
$671,950.00
Summary
A major challenge for transfusion medicine is the constant difficulties in obtaining enough supply of specific red blood cell (RBC) subtypes. In this proposal, we will identify the key steps of enucleation (extrusion of nucleus), a rate limiting process for the in vitro production of RBCs. A better understanding of this process will lead to improved strategies for the efficient and rapid production of self-generated RBCs for individual patient transfusion.
The BHLH Transcription Factor LYL1 In Normal And Leukemic Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$520,945.00
Summary
This project aims to understand how two closely related genes, called SCL and LYL1, work together to control the production of normal red blood cells and when abnormally expressed, cause cancer of the white blood cells. We will specifcially examine how LYL1 causes a specific type of leukemia in children and determine blocking the function of LYL1 will be a useful way to kill leukemia cells.
Sickle cell anaemia and ?-thalassaemia are debilitating diseases for which there is no effective treatment. Patients require lifetime blood transfusions and drugs with significant side effects. These diseases are ameliorated in patients that express foetal haemoglobin into adulthood. The goal of this research is to understand how foetal haemoglobin is normally turned off at birth. This will ultimately help us discover how to switch it back on to treat patients.