Store Operated Ca2+ Entry In Skeletal Fibres From Normal And Dystrophin-deficient Muscle.
Funder
National Health and Medical Research Council
Funding Amount
$351,790.00
Summary
Skeletal muscle, the most abundant tissue in the body, is essential for life and movement. Muscle function is regulated in a complex manner by calcium and is severely impaired in patients with Duchenne muscular dystrophy. Changes in calcium regulation, known to occur in dystrophic muscle, will be investigated in an animal model using a novel, single cell approach. Results obtained will contribute to understanding better muscular dystrophy and help provide therapeutic targets for treatment.
Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, litt ....Pain associated with bone cancer, fractures, osteoporosis, osteoarthritis, osteomyelitis (and other bone infections) often presents the clinician with a difficult problem of treatment as the pain can be debilitating and intractable. Most current treatments for bone pain are based on the assumption that the neural mechanisms underlying pain from different sources, whether it be visceral, cutaneous, muscular or bony, are the same, and can therefore be targeted with similar therapies. However, little is known of the response properties, structure and organization of receptors and neurones responding to, and relaying information about painful stimuli, from bone to the brain. The objectives of this project are to reveal the fundamental neural mechanisms that account for the perception of bone pain. The project will test a series of specific hypotheses in order to explain why bone pain is often poorly controlled by standard pharmacological or surgical approaches. It is expected that this study will reveal the neural mechanisms responsible for relaying sensory information, in particular, that regarding painful stimuli, from bone to the brain. It will lead to a better understanding of the mechanisms of bone pain and form the template for future studies of its treatment.Read moreRead less
Mechanisms Defining Microfibril And Elastic Fibre Assembly, Structure And Function.
Funder
National Health and Medical Research Council
Funding Amount
$619,721.00
Summary
Elastic fibres are important in tissues such as arteries, lung and skin where they provide elasticity. Disruption of their normal structure and function is a major aspect of common diseases such as atherosclerosis, aneurisms, heart valve prolapse, emphysema, and the congenital disorder, Marfan syndrome. Elastic fibres consist of a core of the protein elastin surrounded by 12 nm glycoprotein microfibrils. During development the microfibrils always appear before the elastin and seem to act as a sc ....Elastic fibres are important in tissues such as arteries, lung and skin where they provide elasticity. Disruption of their normal structure and function is a major aspect of common diseases such as atherosclerosis, aneurisms, heart valve prolapse, emphysema, and the congenital disorder, Marfan syndrome. Elastic fibres consist of a core of the protein elastin surrounded by 12 nm glycoprotein microfibrils. During development the microfibrils always appear before the elastin and seem to act as a scaffold for the deposition of its precursor, tropoelastin. However knowledge of the role of each glycoprotein in the assembly, architecture, function and cell biology of microfibrils and elastic fibres is still very limited. Our laboratory has identified, cloned and characterised several microfibrillar proteins and we are uniquely placed to exploit our expertise and unique range of research tools to elucidate the mechanisms involved in the above processes. The Specific Aims are to determine a) the roles of individual components and associated proteins in microfibril and elastic fibre biology b) the architecture of microfibrils and the relationship of their structural heterogeneity to function during tissue development, c) the mechanisms responsible for microfibril and elastic fibre assembly, and other microfibril interactions with the cell surface, d) the gene regulatory mechanisms controlling expression of individual microfibrillar proteins and e) causative mutations of non-fibrillin genes in Marfan-like congenital disorders. The research will greatly increase our fundamental knowledge of the factors controlling the complex molecular mechanisms involved in microfibril assembly and elastic fibre formation, including the roles of individual microfibril-associated proteins, cell surface receptors, cellular processing, and gene regulation of these processes during normal development, which is essential before the full role of elastic fibres in major diseases can be understood.Read moreRead less