Synthetic biology is providing a huge array of new biological components that can be arranged into circuits and inserted into cells to give them new functions. In parallel to this, huge advances have been made in the field of regenerative medicine,opening up the possibility of implantable cells, tissue or devices that are engineered to restore a loss of function or release a therapeutic factor. Engineering cells with genetic circuitry that allows to process inputs and outputs––in a similar manner to processing inputs and outputs in a computer––could revolutionize medicine by shifting diagnosis, manufacture and dose control into the human body. However, despite the vast potential of curative cell-based therapies that uses synthetic biology, implementation of this grand vision is still highly challenging. Getting synthetic circuitry working in specialized human cells in vivo faces major obstacles, including immune rejection, silencing of synthetic circuitry,unwanted perturbation of cell machinery, and competition for cell resources. In sum,the introduction of synthetic circuits to human cells tends to engender dysfunction or cell death.
The field of regenerative medicine is ideally positioned to meet the grand challenge of designing tissues de novo and to deliver innovative solutions to overcome these obstacles. Stem cell reprogramming and differentiation into a huge diversity of human tissue types has been achieved in recent years. An ability to reproducibly generate and culture primary human cells in large numbers means that synthetic circuit libraries can be screened in a high throughput fashion and optimised in environments that closely approximate their destined clinical setting. In turn, synthetic biology has the potential to provide solutions to the big challenges facing regenerative medicine.One example of a barrier that undermines the success of regenerative therapies in all organs and disease contexts is the phenomenon of graft ischemia. Graft ischemia arises during the initial period of cell transplantation due to the limited integration of the cells with the host vasculature resulting in poor supply of oxygen and nutrients to the graft. Up to 90% of implanted cells are lost due to ischemic cell death, and this challenge limits the therapeutic potential of cardiac, liver, pancreatic, and neuronal cell types, among many others. We are therefore proposing two goals:
1) Tackle the specific challenge of ischemic graft cell death (as a universal barrier to cell-therapy and tissue engineering)
2) Establish cores of expertise to promote Canadian leadership at the interface between synthetic biology and regenerative medicine. We will achieve these goals by establishing a synthetic biology–regenerative medicine hub. This hub will make the tools and techniques of synthetic biology readily available to regenerative medicine investigators and enable synthetic biologists to develop and screen their tools in clinically relevant contexts. Fundamentally, it will create expertise cores that are shared among investigators –enabling the initiative to be easily expanded and extended to more investigators. Solving the ischemia problem will be used to initially consolidate the hub around a challenge of universal interest in the first 2-5years. Our ten and twenty-year vision is a Canadian-driven, globally leading, Centre for the Design of Novel Human Tissues.