Understanding Transcription Factor Interactions In Blood Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
All blood cells develop from the same parent cells, which are known as stem cells. Once the decision is made for a stem cell to develop into a particular type of blood cell, mechanisms must exist that ensure the cell only expresses the genes that are appropriate for that cell type. These mechanisms involve the action of proteins known as transcription factors, which specifically activate the expression of the correct genes. While deregulation of these control mechanisms often leads to diseases s ....All blood cells develop from the same parent cells, which are known as stem cells. Once the decision is made for a stem cell to develop into a particular type of blood cell, mechanisms must exist that ensure the cell only expresses the genes that are appropriate for that cell type. These mechanisms involve the action of proteins known as transcription factors, which specifically activate the expression of the correct genes. While deregulation of these control mechanisms often leads to diseases such as cancer, unfortunately our understanding of how networks of transcription factors combine to direct processes such as blood cell development is relatively poor. GATA-1 and PU.1 are essential for the normal development of erythroid and myeloid blood cell types, respectively, and the work in the present proposal is aimed at understanding some of the molecular details of how direct interactions between these two proteins modulate their activity. This information should prove useful in understanding other transcriptionally regulated systems and may eventually help provide a route to treating a number of classes of blood cancer.Read moreRead less
Determining The Role Of Rel/NF-kB Transcription Factors In Myeloid Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$500,944.00
Summary
Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB ....Different types of mature blood cells arise from stem cells in a process involving changes in gene expression that dictate which types of blood cells ultimately develop. A family of gene regulatory proteins called NF-kB transcription factors has been found to control the pattern of gene expression in a particular blood cell precursor called a granulocyte macrophage precursor (GMP) that normally generates two types of mature blood cells called macrophages and neutrophils. In the absence of NF-kB proteins, a change in the pattern of gene expression in GMPs leads to an imbalance in production of these two blood cell types that now favours the generation of neutrophils. This work will provide insight into the molecular mechanisms of blood cell development regulated by NF-kB. With disturbances in the balance of blood cell formation representing a hallmark of leukemia, understanding how this process is normally controlled may have important implications for developing therapeutic strategies to combat various types of leukemias.Read moreRead less
Too few blood platelets leads to fatal haemorrhage, and patients with low platelet counts require transfusions to prevent bleeding. We have recently discovered the key to keeping platelets alive, and now propose the critical experiments which will teach us how to manipulate it and allow platelets to live longer. Our team leads the world in this field. If successful we expect to improve blood bank platelet storage, and boost the supply of platelets available to patients in need of transfusion.
Removal of the nucleus from red blood cells (enucleation) is essential for proper circulation of red blood cells through the microvasculature and high haemoglobin concentration in the blood. How this fundamental process is achieved is surprisingly poorly understood. Here we propose to investigate how enucleation occurs in light of enucleation being an unusual asymmetric division. These studies are likely to lead to improvements in expansion of human red blood cells in vitro for transfusions.
Investigation Of A New Rheology Dependent Platelet Aggregation Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$509,447.00
Summary
We plan to examine a new mechanism promoting blood clot formation that involves the clumping (aggregation) of blood platelets. Our central hypothesis is that disturbances of blood flow, as occurs in diseased arteries, activates this clotting mechanism through a unique platelet activation process. Defining this new activation mechanism has the potential to lead to new approaches to prevent blood clot formation in patients with heart disease.
Activation Transcription Factor-4: Novel Regulator Of Smooth Muscle Cell Repair And Intimal Thickening Through Tenascin C
Funder
National Health and Medical Research Council
Funding Amount
$228,313.00
Summary
CVD represents the most important cause of morbidity and mortality in the world, accounting for 35% of all deaths in Australia. Smooth muscle cell growth accounts for a range of vascular proliferative disorders. This project focuses on understanding the role of ATF-4 as a new key regulator of SMC proliferation and intimal thickening in injured vessels. Moreover, strategies targeting ATF-4 will facilitate future therapeutic strategies to control intimal thickening in patients with vascular diseas ....CVD represents the most important cause of morbidity and mortality in the world, accounting for 35% of all deaths in Australia. Smooth muscle cell growth accounts for a range of vascular proliferative disorders. This project focuses on understanding the role of ATF-4 as a new key regulator of SMC proliferation and intimal thickening in injured vessels. Moreover, strategies targeting ATF-4 will facilitate future therapeutic strategies to control intimal thickening in patients with vascular disease.Read moreRead less