Regenerative medicine is a branch of translational research aiming to replace, engineer or regenerate human cells, tissues and organs to re-establish normal function. Since this entire process occurs naturally during the repair of tissues by the activation of adult stem cells after injury, the knowledge gained from their study will accelerate regenerative medicine. The remarkable capacity of tissue regeneration is illustrated by the activity of the muscle stem cell, which is normally a rare cell resting within muscle, but is rapidly activated in response to injury to expand a population of muscle cells needed for repair. Nevertheless, skeletal muscle remains affected by untreatable muscle disease. These diseases, including muscular dystrophies and muscle wasting associated with cancer or aging, are associated with a decline in stem cell function.
We therefore aim to further regenerative medicine based approaches by discovering novel mechanisms regulating muscle stem cells. The central dogma of molecular biology states that DNA makes proteins through an RNA intermediate. We focus on mechanisms that regulate the final step, the ‘translation' of RNA to protein (otherwise known as protein synthesis), a previously underappreciated aspect of gene regulation that is readily targetable by pharmacological strategies. We will investigate whether certain proteins are selectively synthesized to maintain the ‘stemness' properties of muscle stem cells, and whether the mechanisms that ensure selective protein synthesis are altered in the environment of aging muscle, leading to loss of muscle stem cell function.