Grant: CIHR Fellowship

Stem cells hold huge promise for regenerating damage from both disease and injury. Their use is restricted, however, by difficulties in getting and growing them. They also often behave unpredictably, in part because the instructions they follow are only partially understood. Recently invented methods have made editing the cellular instruction manual, their DNA, possible. This makes the creation of cells with similar properties and known controls feasible. The first part of our proposal is to develop new controls for cell survival and growth using editing techniques. Controlling cell survival and growth is a critical safety measure to make sure that any cell therapy doesn't become cancer. Specifically, we will place proteins capable of killing the cell under the control of a defined chemical, and proteins which prevent the cell from growing under the control of light. This will make the cells unable to form a tumour inside the body, and able to be killed using a known drug if it should be needed. We will also use these edited cells to stress test our control mechanisms and improve their reliability. The second part of our proposal is to make stem cell-like cells that are simple to grow and can be easily converted into useful cell types. To do so we will take normal cells that can be grown without difficulties, and install switches into them that activate the proteins necessary to make them into brain, heart, and liver cells when exposed to specific chemicals. We will also characterize how efficiently these switches work both when on their own, and when put together. Finally, we will put these same switches under the control of proteins that they might encounter in the body. This would be a first step in making cells able to automatically detect damage and effect repair. Overall, this project will provide proof-of-concept for the creation of designer stem cell-like cells with novel therapeutic properties.