Molecular Regulation Of Replicative Lifespan; Implications In Carcinogenesis And Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
The lifespan of normal cells in the body is limited by the number of times they can replicate. In contrast, cancer cells can replicate indefinitely – they are immortal. Our proposed investigations will determine how the mechanisms that control cell lifespan become dysfunctional as normal cells evolve into cancer cells. Understanding these mechanisms will enable the development of new anti-cancer drugs that will reverse cell immortality and halt the replication of cancer cells.
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.
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.
The Function Of BHLH Factors In Adult Haemopoiseis
Funder
National Health and Medical Research Council
Funding Amount
$595,353.00
Summary
Understanding how genes control the behaviour of bone marrow stem cells is currently needed for improving recovery after chemotherapy or bone marrow transplantation and in the future, will aid the application of new stem cell-based therapies for human diseases such as leukaemia. This research will examine how 2 closely related genes control bone marrow stem cell growth and the decision between beocoming a red cell or a white cell.