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
KLFs are master control genes that regulate the expression of many target genes to determine cell fate and to convert one cell fate to another. Mutations in KLFs cause human diseases. This grant will focus on the founding member of the KLF family, KLF1. We will use genomics techniques and animal models to determine how KLF1 works in normal blood cell production and in disease
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