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Medicine by Design’s Grand Questions Program aims to change the future of regenerative medicine through research that addresses some of the field’s biggest unanswered questions.

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Through this program, Medicine by Design is investing in bold ideas and developing transformative and revolutionary solutions that will be of critical importance to regenerative medicine over the next 20 years. These solutions will enable new therapies that promise dramatically better health outcomes for people around the world, ensuring Toronto and Canada continue to lead this health-care transformation.

Medicine by Design is investing $3 million in the Grand Questions Program over the period of spring 2021- spring 2023.

Watch the Grand Questions announcement and panel recording

On May 7, 2021, Medicine by Design hosted an event to announce the funded projects. The event featured a panel discussion called, Ambitious and provocative — expanding the frontiers of regenerative medicine.

Grand Questions Funded Projects

Grand Question: Designing Tissues de novo — Can we make tissues that perform better than nature?

Mimicking the function of the native tissue is often the goal of regenerative medicine research and respects evolutionary pressure. But can we do better?

Can we generate cells and/or tissues that will provide function(s) that are enhanced, entirely novel or “borrowed” from nature (i.e. from non-human organisms) for therapeutic purposes?  Examples of new functional properties could include the ability to evade infection by viruses or other pathogens, enhanced vision (widened spectra), improved sense of smell or hearing, avoidance of senescence and neoplasia.

Is there a way we can design robust cells and tissues such that when they and we eventually expire, we do so painlessly and naturally, without having suffered debilitating conditions?

These outcomes could be achieved by creating chimeric cells, combining tissue functions in one novel cell type, or interfacing cells and tissues with electronics or soft robotics. The new cell/tissue could be designed for ad hoc use (i.e. something that could be removed once the outcome has been achieved), or it could be implanted for life.

Since the development of such a cell/tissue has ethical implications, competitive proposals will integrate ethical considerations and engage with bioethicists to create a consensus framework as part of the project. Competitive applications will propose goals that are well beyond the current state of the art.

Project: Establishing a ‘Centre for the Design of Novel Human Tissues’ to address graft cell death and promote ‘super-tissue’ development

Lead Investigator:
Michael Garton, Assistant Professor, Institute of Biomedical Engineering, University of Toronto

Co-Investigators:
Michael Laflamme, University Health Network
Yun Li, The Hospital for Sick Children
Maria Cristina Nostro, University Health Network
Shinichiro Ogawa, University Health Network
Stephanie Protze, University Health Network

Advisors:
Bruce Conklin, University of California San Francisco
Martin Fussenegger, ETH Zürich
Ron Weiss, Massachusetts Institute of Technology

Grand Question: Physics of Regeneration — What are the core physio-chemical principles governing organ formation, and can they facilitate organ regeneration?

Tissue engineering currently relies in large part on mimicking normal developmental processes in an in vitro setting. Often, small and rapidly developing systems the size of early embryos (e.g. cell aggregates, embryoid bodies and organoids) are used as paradigms for tissue or organ construction. However, to rationally advance the generation of functional post-natal tissues, completely different size and time scales need to be mastered by employing insights and technologies that do not currently exist. During organogenesis, cell differentiation and tissue morphogenesis are spatiotemporally coupled and regulated by biochemical and physical cues.

In contrast to current approaches such as trial-and-error experimentation, it may be more efficient to define conserved physical rules that drive key morphogenetic processes as systems transit to larger sizes and progressively acquire different mechanical features.

Can the physical and chemical principles of embryonic morphogenesis be distilled into core principles and applied to bridge the spatiotemporal gap from organogenesis to the generation of functional organs? Defining these core physical rules and applying them in vitro and in vivo will require close collaboration between developmental and cell biologists with physicists, mathematicians, and engineers.

Project: Defining biophysical mechanisms of organogenesis to facilitate regeneration 

Lead investigator:
Sevan Hopyan, Orthopaedic Surgeon and Senior Scientist, The Hospital for Sick Children

Co-investigators:
Sidhartha Goyal, University of Toronto
Yu Sun, University of Toronto
Rudolf Winklbauer, University of Toronto

Advisors:
Eric Siggia, The Rockefeller University 

Grand Question: New Technology for Cell Tracking — Can we record the signaling history of a cell?

Observing a tissue as it undergoes a dynamic transition (e.g. during development, disease progression or during the integration of regenerated tissue) is challenging, if not impossible, to do using current methods. The capacity to spatially and temporally record cellular signalling events in a multiplexed manner would transform our understanding of the cellular heterogeneity and multicellular information processing that underlies normal and pathological tissue biology.

Can we comprehensively trace the input signals (type, magnitude, duration) that drive cell decision-making in complex multicellular systems undergoing organizational and fate transitions? Can we develop a scalable, high-content and non-destructive technique to log signalling pathways at single-cell resolution in space and time?

Project: Logging cell experience to learn how to program cell function 

Lead investigator:
Alison McGuigan, Professor, Department of Chemical Engineering and Applied Chemistry and Institute of Biomedical Engineering, University of Toronto

Co-investigators:
Gary Bader, University of Toronto
Leo Chou, University of Toronto
Michael Garton, University of Toronto
Hartland Jackson, Sinai Health
Tracy McGaha, University of Toronto
Andrew Woolley, University of Toronto

Advisors:
Fei Chen, Massachusetts Institute of Technology
Trey Ideker, University of California San Diego
Harris Wang, Columbia University

Grand Question: Affordability and Accessibility — How can we make regenerative medicine available to everyone?

Regenerative medicine and cell-based therapies have the potential to cure otherwise intractable diseases and are among the most promising domains for the delivery of paradigm-changing health care. However, the anticipated cost of these therapies will strain even well-resourced health-care systems. Globally, these costs will pose a much greater challenge, with most people not expected to be able to access the benefits of these technologies. Furthermore, it is expected that such technologies, as currently envisioned, will be hard to implement outside major medical centres.

Reducing the cost of developing and delivering these advanced therapies is critical for patient access, but also for researchers and innovators in the field.  Society’s continued investment in research is critical to bringing their products to market. Reducing the barriers to access is a separate but equally critical task.

While some regenerative medicine therapies are based on approaches that do not involve cells, for cell-based therapies can we look to automation, robotics, machine learning or other technologies to simplify their scale-up or scale-out, perhaps making them no more complex than dialysis or chemotherapy?

The development of such technologies will require perspectives from global health practitioners among others with a health accessibility perspective. Therefore, competitive applications will integrate an array of disciplines to inform the team on how best to reach the goal of affordable, accessible regenerative medicine.

Project: On-demand cell therapies for affordable patient access in Canada

Lead Investigator: ​
Keith Pardee​, Assistant Professor, Leslie Dan Faculty of Pharmacy, University of Toronto

Co-Investigators: ​
Leo Chou, University of Toronto​
Shana Kelley, University of Toronto​
Teodor Veres, University of Toronto, ​National Research Council Canada​

​Advisors: ​
Laszlo Radvanyi, Ontario Institute ​for Cancer Research​
Wilson Wong, Boston University