This established team of investigators will research into the molecular control of white blood cell formation and function, using a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes. The team will also attempt to identify new validated targets for therapeutic intervention by using both forward and reverse genetic approaches in mice coupled with complete phenotypic analyses of the blood cell system.
Investigating The Formation And Utility Of The Prenatal Platelet Forming System
Funder
National Health and Medical Research Council
Funding Amount
$793,442.00
Summary
A major challenge to regenerative medicine is discovering how to produce useful cell types in the laboratory. Particularly urgent is the need to generate large numbers of platelets, the building blocks of the clotting system, for clinical use. Current laboratory methods are woefully inefficient, thus cannot meet demand. This project aims to discover how platelets are made in nature. With this information we will be able to devise better platelet production strategies in the laboratory.
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
Understanding The Ancestry Of De Novo Blood Formation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$484,666.00
Summary
Current laboratory methods rely on a hit-or-miss approach for the production of such cells, making the prospect of producing patient-specific cells an inefficient/financially prohibitive process. This project aims to generate new knowledge into when and how fate of early blood cells in selected in nature. With this information we will be able to devise effective blood progenitor cell production strategies in the laboratory.
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.
Dysfunctional blood vessel growth is an important mechanism of many congenital vascular diseases and other postnatal diseases such as ischemia and cancer. Cerebral cavernous malformations (CCMs) are common vascular disease in brain that cause strokes and seizures in midlife. Due to their location in the brain, CCMs are virtually untreatable, making the development of novel therapies a priority. This proposal aims to understand how the molecular players underlying this brain vascular disease cont ....Dysfunctional blood vessel growth is an important mechanism of many congenital vascular diseases and other postnatal diseases such as ischemia and cancer. Cerebral cavernous malformations (CCMs) are common vascular disease in brain that cause strokes and seizures in midlife. Due to their location in the brain, CCMs are virtually untreatable, making the development of novel therapies a priority. This proposal aims to understand how the molecular players underlying this brain vascular disease control blood vessel function and growth.Read moreRead less
Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal c ....Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal cellular differentiation is crucial. The studies outlined here aim to contribute to the understanding of the these processes and hence help to provide the framework for future studies aimed at more directly altering cell fate decision for clinical applications. Read moreRead less