Characterization Of The FHL Protein Family In Striated Muscle
Funder
National Health and Medical Research Council
Funding Amount
$500,750.00
Summary
This grant examines the role of a family of muscle proteins, called FHL proteins, in skeletal and heart muscle. Inherited muscular disorders such as muscular dystrophy and myopathies, cause muscle weakness, which may be profound and lead to premature death due to respiratory muscle failure, or cause mild weakness later in life. The proteins which are defective in these muscular dystrophies are structural muscle proteins, which link and stabilize the contractile fibres in muscle and protect the m ....This grant examines the role of a family of muscle proteins, called FHL proteins, in skeletal and heart muscle. Inherited muscular disorders such as muscular dystrophy and myopathies, cause muscle weakness, which may be profound and lead to premature death due to respiratory muscle failure, or cause mild weakness later in life. The proteins which are defective in these muscular dystrophies are structural muscle proteins, which link and stabilize the contractile fibres in muscle and protect the muscle from the stresses and damage resulting from repeated muscular contraction. We have identified that the FHL proteins, which are the focus of this grant application, bind to and potentially regulate muscle proteins, which have been shown to cause forms of muscular dystrophy and cardiomyopathy. Examination of these interactions will provide insights into the biological mechanism of these muscle disorders. Furthermore, one of these proteins, FHL1 is significantly increased in hypertrophic cardiomyopathy, heart muscle thickening, a major cause of sudden cardiac death in young adults. We are creating transgenic mice, which make increased levels of FHL1 protein in their heart muscle, to determine whether increased FHL1, by itself is sufficient to promote heart muscle thickening. These studies should lead to further understanding of the development of diseases of heart and skeletal muscle, which may lead to novel treatments in the future.Read moreRead less
Maintenance of skeletal muscle integrity is critical for normal locomotor function. During adulthood skeletal muscle mass and strength is progressively lost which leads to locomotor impairment common in the elderly. Loss of skeletal muscle may also contribute to functional impairment in patients with inherited disorders of the scaffolding connective tissue that hold muscle fibres together, such as Duchenne's dystrophy. Understanding the biology of muscle cell growth and responses to environmenta ....Maintenance of skeletal muscle integrity is critical for normal locomotor function. During adulthood skeletal muscle mass and strength is progressively lost which leads to locomotor impairment common in the elderly. Loss of skeletal muscle may also contribute to functional impairment in patients with inherited disorders of the scaffolding connective tissue that hold muscle fibres together, such as Duchenne's dystrophy. Understanding the biology of muscle cell growth and responses to environmental stresses such as exercise and ageing is, therefore, critical to healthy daily functioning. In preliminary studies we have defined a novel biochemical pathway which we believe underlies the ability of muscle to grow larger and stronger. In this application, we propose to rigorously evaluate the role of this pathway in muscle growth by experiments performed both with cell culture models and in animals. The findings of this study would have direct therapeutic benefit for a large number of major clinical conditions, such as heart failure, age-related muscular weakness and muscle diseases.Read moreRead less
Optimizing Implanted Cell Survival Using A Tissue Engineering Model
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
Cell therapy and tissue engineering involve the insertion of specific cells into damaged tissues or into a bioraector in a patient's body to generate new replacement tissues. This project seeks to improve two factors associated with inserting cells : 1. The innate survival characteristics of the cells being inserted, and 2. The blood vessel supply at the site of insertion. These techniques will greatly improve the survival of inserted cells.
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.
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
Analysis Of T Cell Fate Regulation By Asymmetric Cell Division
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
The aim of this research is to study how white blood cell growth is regulated by signals of the immune system. Problems in this process can have drastic effects on the well being of an individual leading to deficiencies in controlling infection and development of diseases such as cancer. Once we understand how these signals regulate white blood cell growth, we can begin to develop therapies to provide protection against these diseases.