Molecular pathology of collagen VI-related muscular dystrophies [ 2004 - 2006 ]

Research Grant

Researchers: A/Pr Shireen Lamande (Principal investigator) ,  Prof John Bateman ,  Prof Kathryn North

Brief description The inherited muscular dystrophies, characterised by progressive muscle weakness and wasting, are a significant cause of physical disability. Muscle cells are anchored into the surrounding tissue by a chain of interacting proteins. Proteins inside the cell link to cell surface proteins, which in turn link to extracellular matrix proteins. If any one of the links is broken by a mutation, the connection is lost and muscle disease results. Most studies to date have focused on the role of intracellular and cell surface proteins, and relatively little attention has been paid to the extracellular matrix proteins. Mutations in the extracellular matrix protein collagen VI have been found in patients with Bethlem myopathy and Ullrich muscular dystrophy. These mutations tell us that collagen VI plays a critical role in muscle but we don't know how the mutations break the link between the cell and the matrix or why they cause a muscle disease. We will look for collagen VI mutations in our group of new Bethlem myopathy and Ullrich patients, and perform detailed studies on the effect of the mutations on collagen VI production, structure and function. These studies will allow us to provide accurate diagnosis and genetic counselling for affected individuals and begin to tell us how the mutations break the cell-matrix link. Mutations in other extracellular matrix proteins that interact with collagen VI are also likely to cause muscular dystrophies. One of these proteins is biglycan. We know from studies in mice that when biglycan is missing the mice have muscular dystrophy, so it is likely that some human muscular dystrophy patients have biglycan mutations. We will look for biglycan mutations in patients with muscular dystrophies and perform detailed studies to try to understand the effect of the mutations on the biglycan protein. This application brings together two groups with complementary expertise, to further our understanding of the basis of muscular dystrophies.

Funding Amount $AUD 574,500.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant