Snail Family Proteins Regulate Stem Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$288,650.00
Summary
This research aims to discover the role of a family of genes in regulating stem cells. These genes are known to turn other genes off and we have shown that this family is required to maintain stem cells in animal tissues. The current research seeks to determine which genes are normally switched off in order to maintain normal stem cells. We also aim to determine if turning these genes on leads to cancer formation.
Role Of Beta-catenin And Its Regulator FAM In Haemopoietic Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$506,500.00
Summary
Haemopoietic stem cells (HSC) are currently the best characterised adult stem cell (SC) population and currently the only SC population used in cellular therapy. Adult HSC reside in the bone marrow and it is generally accepted that these rare cells cycle slowly and maintain themselves by a process involving self renewal. The cellular physiology that underlies HSC self renewal is still to be defined and no single factor has been described which is able to induce substantial proliferation and expa ....Haemopoietic stem cells (HSC) are currently the best characterised adult stem cell (SC) population and currently the only SC population used in cellular therapy. Adult HSC reside in the bone marrow and it is generally accepted that these rare cells cycle slowly and maintain themselves by a process involving self renewal. The cellular physiology that underlies HSC self renewal is still to be defined and no single factor has been described which is able to induce substantial proliferation and expansion of HSC in a defined system while maintaining critical stem cell properties. Like other SC, a critical characteristic of the rare HSC population of cells is their ability to maintain their unique stem cell properties in vivo (the process of self-renewal) while generating more committed cells which will form large numbers of differentiated and specialized mature blood cells. Recent evidence that HSC can repair other organs under some circumstances raises the possibility that this adult SC population could provide an alternative to embryonic stem cells for many stem cell therapies. If this is the case the therapeutic application of HSC becomes significantly broader. Critical to development of such applications will be an understanding of HSC self renewal and development and new approaches to expand this limited cell population. Major progress in this area will require the definition of both the intrinsic and extrinsic mechanisms that control HSC maintenance and self-renewal. Any findings in this area will have major clinical significance and be of enormous benefit to the community. Here we focus on the role of a known intrinsic regulator of SC behaviour (beta-catenin) with the aim of establishing its role in the maintenance of HSC and its regulation by a novel cofactor (FAM). We will determine if the level of beta-catenin is critical in the maintenance and-or differentiation of haemopoietic stem cells and what role FAM plays in this regulation.Read moreRead less
The Developmental Hierarchy Of Haemopoietic Lineage Relationships
Funder
National Health and Medical Research Council
Funding Amount
$192,000.00
Summary
The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood ....The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood cell progeny with each other and thus to provide a lineage map of the system. To do this we will isolate precursors at various stages along the developmental pathways and determine their capabilities to produce the normal range of progeny. We will then use a number of genetically altered mouse strains to assess the genes involved in this process. These studies will help provide an underlying scientific basis to the attempts to development a number of stem cell therapies that are aimed at boosting or directing stem cell production in procedures such as bone marrow transplantation for leukemia and immune deficiency. In addition a number of characterized human blood malignancies seem to have developed along aberrant pathways indicating that inappropriate lineage specification may be a factor in cancer.Read moreRead less
Interactions Between Transcription Factor Networks And Cell Signaling Pathways During Early Blood Development
Funder
National Health and Medical Research Council
Funding Amount
$589,338.00
Summary
Cancer initiating cells acquire stem cell characteristics and self renew within a supportive environment that helps maintain and propagate malignant tumours. Identifying the normal hierarchy of gene regulation within blood stem cells and designing therapies that target key transcription factors (proteins that control other genes) that are over expressed in cancer stem cells is the ultimate goal.
Isolation And Characterisation Of Novel Progenitor Cells In The Mammary Epithelium And Their Role During Carcinogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$470,346.00
Summary
Stem and progenitor cells in the breast are the immature cells from which mature cells are derived. Their are long-lived, resistant to death and can produce multiple types of mature cells, implicating them as cells from which breast cancer may originate. We aim to search for novel cell surface markers that define the progenitor cells in the mouse mammary gland. The data gathered from this project may facilitate the development of targeted therapies to the cells of origin in breast cancer.