Analysis Of Factors Governing Globin Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$512,996.00
Summary
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 embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
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 worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.
Structure And Function Of The Alternative Splicing Factor ZNF265
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
Now that the human genome has been sequenced, we can see that a human being is defined bye approximately 30000 genes. One of the biggest surprises to come from this work was that the number of genes was significantly smaller than many predicted. Similar surprise was registered at the discovery that the genome of the fruit fly actually contained fewer genes than that of the model worm, Caenorhabditis elegans. Part of the explanation for these apparent discrepencies lies in the phenomenon known as ....Now that the human genome has been sequenced, we can see that a human being is defined bye approximately 30000 genes. One of the biggest surprises to come from this work was that the number of genes was significantly smaller than many predicted. Similar surprise was registered at the discovery that the genome of the fruit fly actually contained fewer genes than that of the model worm, Caenorhabditis elegans. Part of the explanation for these apparent discrepencies lies in the phenomenon known as gene splicing, whereby one gene can actually give rise to many different isoforms of the same protein. These different isoforms can have different structures and-or functions, and dramatically increase the complexity that it is possible for an organism to achieve with a given number of genes. The process of splicing is very intricate, requiring precise control to allow an organism to develop normally. Many human genetic diseases are known to arise from problems with splicing. However, our understanding of the mechanisms of splicing is rather incomplete. This proposal aims to improve our understanding of the splicing process through a range of biophysical and molecular biological approaches. This information should prove useful in understanding human development and disease.Read moreRead less
Characterisation Of Erythropoietic Mutants Identified In A Forward Genetic Screen In Mice.
Funder
National Health and Medical Research Council
Funding Amount
$501,902.00
Summary
The human bone marrow is the pivotal organ in the replacement of the vast numbers of blood cells normally consumed each day. One of the cells regenerated by this organ are the red blood cells which are critical for the transport of oxygen to the tissues. This proposal uses genetically altered mice to identify genes that are critical for the production of normal red blood cells. Mice exposed to a chemical that induces random mutations in their genome are bred and pups with abnormal red blood cell ....The human bone marrow is the pivotal organ in the replacement of the vast numbers of blood cells normally consumed each day. One of the cells regenerated by this organ are the red blood cells which are critical for the transport of oxygen to the tissues. This proposal uses genetically altered mice to identify genes that are critical for the production of normal red blood cells. Mice exposed to a chemical that induces random mutations in their genome are bred and pups with abnormal red blood cells are identified. The responsible genetic mutation is identified and the gene is then studied to determine how it influences red blood cell production. The results of these studies provide insights into a variety of human conditions including anemia, thalassemia and sickle cell disease.Read moreRead less
STUDIES OF NF-E4, A NOVEL FETAL/ERYTHROID SPECIFIC FACTOR INVOLVED IN FETAL GLOBIN GENE REGULATION
Funder
National Health and Medical Research Council
Funding Amount
$753,810.00
Summary
Sickle cell anemia and thalassemia are the commonest genetic disorders worldwide. Those affected suffer devastating clinical sequelae and mortality in the first twenty years of life remains high. A cure for these diseases is dependent on the replacement of the affected or absent hemoglobin protein chains with normally functioning hemoglobins. This is evident in rare patients who co-inherit a natural mutation which elevates fetal hemoglobin (HbF), as these patients have a dramatically ameliorated ....Sickle cell anemia and thalassemia are the commonest genetic disorders worldwide. Those affected suffer devastating clinical sequelae and mortality in the first twenty years of life remains high. A cure for these diseases is dependent on the replacement of the affected or absent hemoglobin protein chains with normally functioning hemoglobins. This is evident in rare patients who co-inherit a natural mutation which elevates fetal hemoglobin (HbF), as these patients have a dramatically ameliorated clinical course. Therefore, treatment strategies which could reactivate fetal globin gene expression after birth should be explored for these diseases. To achieve this goal we must further our understanding of the normal mechanisms of developmental regulation of globin gene expression. To this end we have recently identified a novel gene which is critical for fetal globin expression. The studies we propose here will further define the function of this gene and assess its potential for gene therapy for sickle cell disease and thalassemia.Read moreRead less
ATR-X Syndrome: Role Of ATRX In Testicular Growth And Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$650,881.00
Summary
Infertility is surprisingly common and affects 1 in 20 Australian men. Testosterone and its receptor, the androgen receptor, are well known to be essential for spermatogenesis and fertility. We have identified an important regulator protein (ATRX) of androgen receptor activity and show that loss of function of ATRX in testes of mice leads to spermatogenesis defects. Identifying the molecular action of ATRX will lead to a better understanding of the underlying causes of infertility in men.