Micro-damage and repair in human skeletal muscle

Much of my research has been on adaptation of human skeletal muscles to exercise. While it is well established that regular exercise leads to precisely tailored muscle adaptations as well as considerable overall health benefits to our bodies, the mechanisms behind the adaptations have proven elusive.

One of the current ideas is that the strain of exercise induces micro-damage at the molecular level in the active muscles. Its repair is crucial to the adaptations observed, which consist of adjustments that are specific to the type of exercise performed.
To this extent, I have developed a set of tools that allows that allow the assessment of micro-damage at the level of individual muscle fibres over the last few years.

The primary micro-damage marker is alpha B crystallin, a small chaperone whose main function is thought to bind to unfolded proteins to block potential sites of aggregation. Our pilot data - based on classic immunohistochemistry and correlative EM - show that in human m. vastus lateralis biopsies, it binds tightly to sites where the regular structure of myofibrils is disturbed. To establish this is the first tasks, using a novel immunohistochemistry approach combined with image processing (deconvolution) developed recently.
Our hypothesis is that different types of exercise lead to different micro-damage patterns. To test this, we have a collection of biopsies taken before and after different types of exercise.

According to our pilots, most of the repair happens relatively fast (minutes to hours) and locally, at the sites of damage within the fibres. To establish this, another series of markers essays for local protein degradation and repair can be used, which have been developed over a several year period.