Grant: CIHR Fellowship

Gene expression is controlled at multiple steps to ensure that proteins are made in the correct time and place. The production of proteins from mRNA blueprints depends exclusively on large molecular machines called ribosomes. Until recently it was believed that ribosomes act in a rote manner to translate mRNAs into proteins. However, our lab showed that cells possess specialized ribosomes with a unique composition that allows them to select when and where certain mRNAs are made into proteins. These specialized ribosomes control the production of a surprising number of master regulators of the cell suggesting that this novel level of control may allow cells to rapidly and directly remodel gene expression. Such rapid remodeling is especially important in the context of wound healing and regeneration where cells must quickly repair, reform and re-pattern damaged tissues while contending with a broad dampening of normal cellular function that accompany acute injury. Studies of protein abundance reveal that limb regeneration in species like the axolotl, a highly regenerative salamander, is accompanied by dynamic expression of distinct ribosome proteins suggesting that injured cells may rapidly assemble specialized ribosomes to mitigate tissue damage. To test this hypothesis, I will use the well-established limb axolotl amputation model to assess changes in protein translation and ribosome composition during limb regeneration and the role of these changes in wound healing and repair. This work will not only define how cells use specialized ribosomes to rapidly respond to injury and stress but also directly identify the core proteins that constitute the tool kit for vertebrate regeneration providing a firm foundation for further studies into how this tool kit may be deployed to promote better wound healing and organ repair due to chronic and acute injuries and degenerative diseases in humans.