Regulation Of Red Blood Cell And Platelet Formation By BHLH Proteins
Funder
National Health and Medical Research Council
Funding Amount
$422,600.00
Summary
Continuous production of normal blood cells by the bone marrow is a process critical to human life. Disruption of this process leads to diseases such as leukemia, aplastic anemia and myelodysplasia which have devastating consequences for affected patients. Pivotal to understanding these diseases is a knowledge of the regulation of normal blood production. Our laboratory works on a gene known as SCL that is critical for blood formation. We have recently shown that loss of SCL in adult bone marrow ....Continuous production of normal blood cells by the bone marrow is a process critical to human life. Disruption of this process leads to diseases such as leukemia, aplastic anemia and myelodysplasia which have devastating consequences for affected patients. Pivotal to understanding these diseases is a knowledge of the regulation of normal blood production. Our laboratory works on a gene known as SCL that is critical for blood formation. We have recently shown that loss of SCL in adult bone marrow leads to abnormalities in two types of blood cells, the red blood cells and the platelets. This grant will extend this important observation to understand how the production of these cells is altered and what is its consequence. Our studies will help clarify the basis of blood cell formation and may impact on how we diagnose and treat a wide variety of blood disorders.Read moreRead less
Klf5 Function In Normal And Leukaemic Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$609,924.00
Summary
Acute Myeloid Leukaemia (AML) is a devastating disease that affects both children and adults. New treatments that target particular genetic abnormalities are urgently needed. We have identified KLF5 as a gene that may control blood cell maturation. In AML patient samples we have found alterations of the KLF5 gene that may suppress its activity and contribute to the formation of leukaemia. These leukaemias may be good candidates for treatment with new drugs called methyltransferase inhibitors.
Modern chemotherapies are designed to exert maximal effect on tumour cells while having minimal side-effects on normal cells. Remarkable advances in our understanding of the molecular biology of cancer has provided possible avenues for more successful targeted cancer treatments. Several crucial interactions between cancer-specific proteins called oncoproteins , occur largely in tumour cells and thus provide ideal targets for intervention. The proposed project is to develop a model system for a t ....Modern chemotherapies are designed to exert maximal effect on tumour cells while having minimal side-effects on normal cells. Remarkable advances in our understanding of the molecular biology of cancer has provided possible avenues for more successful targeted cancer treatments. Several crucial interactions between cancer-specific proteins called oncoproteins , occur largely in tumour cells and thus provide ideal targets for intervention. The proposed project is to develop a model system for a target specific therapy of leukaemia cells by blocking the interactions between oncoproteins. Moreover, the ability to isolate specific blockers of particular protein-protein interactions provides an opportunity to unravel complex genetic pathways in mammalian systems, which are relatively intractable by other analyses. The dissection of pathways using specific blockers may also provide a useful avenue for identifying new drug targets. We have chosen to target particular interactions involving one known oncoprotein in the search for specific inhibitors. A genetic selection will be used to identify random, constrained peptide sequences which are capable of blocking these interactions and which do not interfere with other interactions involving the oncoprotein. This technique allows one to select for or against specific blockers of known interactions from a library containing millions of candidate drug leads in baker's yeast cells. This procedure will be most suitable for high through-put drug screening projects. The validity of this approach to the identification of new peptide drug leads will be finally established in vivo using transgenic models of oncoprotein-dependent cancer in mice.Read moreRead less