Characterisation of a novel family of skeletal muscle gene regulators [ 2003 - 2005 ]

Research Grant

Researchers: Prof Edna Hardeman (Principal investigator) ,  Nanthakumar Subramaniam

Brief description Muscle cells may be broadly divided into two classes, slow- or fast-twitch, with different physiological and biochemical properties. These properties are largely determined by the protein products of several multi-gene families that encode the contractile apparatus characteristic of muscle cells. The pattern of expression of these muscle-specific genes defines a muscle cell as either a slow-twitch or fast-twitch myofibre. Skeletal muscle is inherently plastic in its ability to express different genes in response to altered functional demand, and under certain circumstances, fibres can convert from one type to another. Conditions known to cause myofibre conversion in humans include congenital myopathies, spinal injury, and exercise. We have identified a novel family of proteins that regulate the genes that confer fibre type. In this proposal, we will further characterise the function of each of these proteins in skeletal muscle development and fibre determination. In addition, the gene that encodes these proteins is one of many deleted in the human condition Williams-Beuren Syndrome (WBS). WBS is characterised by supravalvular aortic stenosis (SVAS), neurological and cognitive defects, infantile hypercalcemia, dental malformations, musculoskeletal anomalies and growth retardation with short stature. The musculoskeletal anomalies, including joint contractures, muscular pain and kyphoscoliosis, cause WS patients to lack stamina and fatigue easily. An underlying myopathy has been reported and may account for the physical limitations, however the disease causing gene-genes have not been identified. We predict that a lack of the MusTRD proteins contributes to these conditions. In general, the findings from our study will yield insights that will lead to improved treatments of patients who suffer from muscle disease or have sustained a nerve injury and improved approaches to excercise training.

Funding Amount $AUD 443,250.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant