Fiber-type-specific and activity-regulated gene expression in fast skeletal muscle
Who: Dr. Ken Hastings
Where: McGill University
How: $106, 737 per year for 3 years



The Basic Biology of Fast and Slow

Before neuromuscular disease can be fully understood, we must understand the basic biology of muscle. Part of this fascinating and complex science involves how muscle fibres develop into their two separate varieties: fast and slow.


Many people are surprised to learn that muscle cells come in fast and slow varieties, says Dr. Ken Hastings, a molecular biologist and member of the Neuromuscular Group of the Montreal Neurological Institute of McGill University. Dr. Hastings is investigating the molecular events that determine muscle fibre-type.

"Muscle fibre-type is an important aspect of muscle function," he explains. "These different cell types are physically specialized for different roles. Fast and slow are relative terms based on the rate of contraction once the muscle cell (fibre) is activated."

While evidence shows that the initial fibre-type is somewhat genetically pre-determined, fibre-type is also function-related; the electrical influence of the motor neuron affects the fibre-type of the muscle cells it controls. Muscle cells that are used a lot become slow and those that are not become fast.

In the end, the cell type depends on which proteins the cell manufactures, which depends on which genes it expresses. "So fibre-type is a question of regulated gene expression," says Dr. Hastings.

"The idea of gene families that are differently expressed in different muscle fibres is the heart of what I am studying. How is it that two different muscle fibres, one beside the other, decide to use different members of gene families?"

To decipher fibre-type specific gene regulation, Dr. Hastings studies a gene called the Troponin I fast gene. Troponin can be either fast- or slow-specific, and is the protein involved in regulating muscle contraction. In fact, troponin is needed for muscle to relax. And troponin is the control switch for myacin, the molecular 'motor' of muscle contraction that ultimately determines whether the fibre becomes fast or slow.

Whether a given gene is expressed in a cell is a function of specific DNA sequences called cis-regulatory elements. "Our goal is to find the cis-regulatory elements in the Troponin I fast gene that make it fast fibre-specific," says Dr. Hastings.

Understanding fibre-type's role in muscle function is important to neuromuscular research, says Dr. Hastings, if we want to be able to control muscle regeneration effectively, or, "if we want to maximize the function of residual muscle in the case of disease, it might be beneficial if we could manipulate the fibre-type."

And, he adds, what we learn about how genes work in muscle could be very important in gene therapy. "Right now in gene therapy, the cis-elements are very non-specific, but it may be useful to have more control over the genes.

"If we can identify the cis-elements that control fibre-type specificity, we are going to get somewhere."

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