Regionalisation And Differentiation Of EPL-derived Neurectoderm: Directed Formation Of Dopaminergic Neurons In Vitro.
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
Neurodegenerative diseases result from the loss, damage or dysfunction of neural populations. For example, dopaminergic neurons are lost progressively in Parkinson's Disease. A potential method of treatment is 'cell therapy' which envisages transplantation of cells back to the site of cell loss, and restoration of function. Application of the cell therapy approach is limited by the unavailability of cells for transplantation. Embryonic stem (ES) cells provide a potential solution to this problem ....Neurodegenerative diseases result from the loss, damage or dysfunction of neural populations. For example, dopaminergic neurons are lost progressively in Parkinson's Disease. A potential method of treatment is 'cell therapy' which envisages transplantation of cells back to the site of cell loss, and restoration of function. Application of the cell therapy approach is limited by the unavailability of cells for transplantation. Embryonic stem (ES) cells provide a potential solution to this problem because they can be grown in unlimited numbers and differentiated to any kind of cell that is found in the embryo or adult. In this application we propose to continue our work on controlling the differentiation of ES cells to neural lineages. Production of dopaminergic neurons will be a particular focus. We will establish conditions that enable the production of these cells in a manner that is therapeutically relevant and predicted to be acceptable to regulatory authorities. Cells will be tested by transplantation into adult rats to assess their therapeutic potential, in particular persistence, integration and differentiation within the brain environment. Research required to achieve the production of transplantable cells will also provide basic information about the mechanisms by which the mammalian embryo allocates cells, specifically cells of the nervous system, to specific lineages during embryogenesis. This information will be important for the production of other neural cell types, which have therapeutic potential for treatment of diseases like stroke, motor neuron disease and spinal cord injury.Read moreRead less
Making Human T- And B-lymphocytes For Immunotherapy And Antibody Production
Funder
National Health and Medical Research Council
Funding Amount
$795,880.00
Summary
Lymphocytes are white blood cells that are involved in producing antibodies, killing defective cells, or killing cells infected with viruses. In recent years, researchers have found ways to harness lymphocytes to develop medicines for treating a variety of different cancers. In this project, we will establish methods to make human lymphocytes in the laboratory from stem cells, paving the way for the broader application of this cell type to new therapies.
Reprogramming Human Fibroblasts Into Induced Trophoblast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$889,064.00
Summary
We have been able to generate artificial human trophectoderm which is the tissue that creates the placenta. This will allow us to do research in how the genes control the fate of these cells without the need of human embryos or placenta. We anticipate that the derivation and characterising these cells will revolutionise placenta research, which in turn will contribute to the establishment of new therapies for placenta disease and infertility.
Function Of The Lysophospholipid Receptor Family In Neuronal Stem Cells And Their Progenitors.
Funder
National Health and Medical Research Council
Funding Amount
$380,723.00
Summary
Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor ....Stem cells have the potential to give rise to a vast array of differentiated cells. Neuronal stem cells (NSC) can differentiate into progenitor cells which can themselves differentiate into cells of the nervous system: neurons and macroglial cells (astrocytes, oligodendrocytes, Schwann cells). This in turn can assist in the treatment of degenerative diseases such as multiple sclerosis, Parkinson's disease, motoneuron desease etc. Our project aims to study the effects on NSC and their progenitor cells of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), bioactive molecules known to play an essential role in the nervous system during development and inflammation. Our project aims to understand the mechanisms of action of these molecules in NSC maintenance, proliferation, differentiation and migration. By understanding how these molecules are able to regulate NSC biology will provide new avenues in the development of tools necessary for stem cell therapy.Read moreRead less
The Roles Of Beta-catenin, APC And The Wnt/beta-catenin Pathway In Lens Development And Cataract
Funder
National Health and Medical Research Council
Funding Amount
$456,764.00
Summary
Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epi ....Cataract is a leading cause of blindness. Many risk factors have been identified but the basic cellular and molecular mechanisms that cause cataract are not well understood. Investigation of these mechanisms is essential to identify potential targets for future therapies to arrest or prevent cataract formation. The lens is composed of epithelial and fibre cells. Much of our research has focussed on identifying genes and cell signalling pathways that regulate formation of fibre cells from the epithelial cells. However, considerably less is known about factors that regulate formation of the epithelium itself. As the epithelial cells are affected in some types of cataract it is vitally important to understand the mechanisms that control formation and maintenance of these cells. Our previous studies have identified a growth factor family (TGF-beta) that causes epithelial cataracts. Importantly, our recent studies have identified another growth factor signalling pathway (Wnt-beta-catenin) as being essential for the formation and maintenance of the lens epithelium. We hypothesise that this pathway is disrupted dring cataract formation. This project uses state of the art tools and techniques to investigate the role of two central molecular components of this Wnt pathway (APC and beta-catenin) in the developing lens. By genetically manipulating the activity of these proteins in the mouse lens we will investigate the roles these molecules and the Wnt signalling pathway play in lens development and whether inappropriate activity results in abnormal development or cataract. We will also be able to investigate whether modulating this pathway affects the formation of epithelial cataracts by TGFbeta. The results will provide detailed information on how these molecules regulate lens structure and function and have the potential to identify targets for preventing or ameliorating cataracts.Read moreRead less
Differentiation Therapy Of Acute Myeloid Leukaemia: Combining RAR-agonists And G-CSF.
Funder
National Health and Medical Research Council
Funding Amount
$449,500.00
Summary
The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human le ....The application of cancer treatments that target specific molecules hold significant promise. However to apply these treatments detailed knowledge is required of the how the molecular targets function in cells. Our previous work using normal blood cells has identified two genes ( MAD1 and p27KIP1 ) that are required for the effects of one such targeted treatment that is aimed at the retinoic acid receptor alpha. We propose to test this treatment in mouse models of human leukaemia and in human leukemia cells grown in the laboratory. By deleting the genes for MAD1 and p27KIP1 we will determine if leukaemias lacking these genes fail to respond to treatments targeting the retinoic acid receptor alpha. We will also test if treatments that target retinoic acid receptors in combination with G-CSF, a protein that has previously been demonstrated to have anti-leukaemic activity, can work together to block growth of leukaemic and genetically modified cells. Together these studies will help define classes of leukamias that either will or will not respond to treatments aimed at retinoic acid receptor to better target future leukemia treatments.Read moreRead less
Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
Hematopoietic Transplants From Autologous Pluripotent Cell Sources
Funder
National Health and Medical Research Council
Summary
This proposal investigates the utility of two types of patient-derived stem cells for transplantation into blood. These are induced pluripotent stem cells that are reprogrammed from specialized tissues such as skin cells, and stem cells derived using the genetic material of oocytes or sperm only ( one-parent embryos). Using the mouse, we are looking at the ability of these cells to form normal blood lineages after transplantation, and to repair blood in a mouse model for beta-thalassemia.
Mechanisms Of Premature Cranial Fusion: Role Of Retinol Binding Protein 4 In Osteogenesis And Suture Fusion
Funder
National Health and Medical Research Council
Funding Amount
$555,855.00
Summary
Craniosynostosis is a condition where the skull bones fuse prematurely, affecting skull shape, vision and cognition. It occurs in 1 in 2,500 births. The only treatment is surgery, which is life-threatening, costly and may need to be repeated. By studying how fusion happens in this project we may be able to devise therapies to minimize the risks and need for re-operation. Here, we hope to show that modification of a single substance in the skull of mouse models can prevent premature bone fusion.
ARC, A Newly Identified Regulator Of Chondrocyte Differentiation And Death, Is A Novel Therapeutic Target For OA
Funder
National Health and Medical Research Council
Funding Amount
$763,983.00
Summary
We have identified a critical regulator of the survival and normal metabolism of the cells in articular cartilage. Loss of this molecule is an early event in joint injury that leads to osteoarthritis (OA). The current proposal will determine the mechanisms whereby this protein functions to protect cartilage breakdown in OA, how its levels in chondrocytes are regulated in both healthy and diseased conditions, and at what stages of disease increasing its expression protects against OA progression.