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.

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 will invest up to $3 million in the Grand Questions Program. Successful teams will receive up to $1 million each over the period of March 1, 2021- August 31, 2022.

NEXT KEY DATE: Phase 1 proposals due Aug. 21, 2020

Overview

Medicine by Design invites researchers to submit proposals outlining how they will address one of the following Grand Questions. These questions have been developed and refined in consultation with investigators at U of T and its affiliated hospitals and Medicine by Design’s Scientific Advisory Board.

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.

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.

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?

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.

Current approaches to reverse aging focus on limiting cell senescence, promoting and ensuring mitochondrial health, rejuvenating factors, epigenetic reprogramming, and modulating the immune and stress environment. Can we vastly improve on current approaches to prevent aging, or develop new concepts and propose novel technologies that in turn will reverse the inevitable process of aging and increase human healthy lifespan?

The goal of this question is to better understand the aging process, identify new mechanisms of aging, and develop strategies that have the potential to reverse it. One approach could be to determine the minimum and maximum heathy lifespan value of a particular species. Is there a master regulator or set point of lifespan value? Does this master regulator influence or even determine metabolic activity and biosynthetic capacity, the ability to repair oxidative and DNA damage and maintain organelle health, telomere erosion and response to stress? An approach to addressing these questions could explore new concepts and propose novel technologies that have the potential to vastly improve on strategies to promote organismal health within the lifespan range and reverse the inevitable process of aging.

Other perspectives include considering whether repairing aged stem cell function not only involves restoring “young” intrinsic repair and epigenetic regulatory pathways, but also requires at the same time repairing the niche and preventing the influence of damaging systemic factors. Alternatively, one can ask if cancer is an inevitable consequence of healthy aging or if we can separate the two.

Until very recently, the concept of an irreversibly failing organ was accepted and not challenged. But what if this dogma was wrong? What if the presumed irreversible permanent tissue damage could be reversed, and strategies could be implemented that would allow for organ regeneration?

Is it possible to unravel the path to re-program endogenous cells to clear scar tissue and regenerate parenchyma? Such capability could result in an unprecedented paradigm shift in the clinical management of end-stage organ failure. Physicians would be able to block disease progression (e.g., fibrosis) at earlier stages of disease and ultimately induce functional tissue (organ specific parenchyma) regeneration in both native and transplant organs.

With the global population aging and the incidence of chronic disease rising, reversal of scar tissue and regeneration of parenchyma would have an unprecedented impact on patient survival and quality of life, benefitting healthcare systems globally in an unprecedented way.

Key Dates

Research funding for the Grand Questions will include two phases. Teams that are successful at Phase 1 will have access to $10,000 from September to October 2020 to develop the team and the Phase 2 proposal. Teams that are awarded Phase 2 funding will receive up to $1 million each. The funding period will be March 1, 2021, to August 31, 2022.

Milestone Who Date
Phase 1 proposals due Applicants August 21, 2020
Phase 1 proposals reviewed
Successful proposals awarded Phase 1 funding
Scientific Advisory Board September 2020
Teams develop Phase 2 proposals Applicants September-November 2020
Phase 2 proposals due Applicants November 13, 2020
Phase 2 proposals reviewed by external reviewers
Phase 2 funding awarded to successful teams
External reviewers
Scientific Advisory Board
December 2020-February 2021
Funding period
March 2021 – August 2022

Eligibility

Investigators with a faculty appointment at the University of Toronto are eligible to apply.

Medicine by Design Cycle 2 lead principal investigators (PI) are not eligible to be lead PIs for projects funded under this program, but are eligible to be co-PIs. Cycle 2 co-PIs and all other investigators who have previously received Medicine by Design funding are eligible to be lead PIs for this program.

Only one application will be accepted from each lead investigator. Each project may have only one lead PI but there is no limit to the number of co-PIs.

Multiple teams may submit proposals around the same Grand Question. Not all Grand Questions will receive funding.

Equity, Diversity and Inclusion

The University of Toronto recognizes that diversity is essential to the creation of a vibrant intellectual community that allows our researchers to maximize their creativity and their contributions. Medicine by Design is therefore strongly committed to diversity in research and especially welcomes applications that engage racialized persons/persons of colour, women, Indigenous/Aboriginal Peoples of North America, persons with disabilities, LGBTQ+ persons, and others who may contribute to the further diversification of ideas.

All applicants (both lead and co-PIs) are required to answer a self-identification survey. In completing this survey, applicants may voluntarily self-identify in all applicable groups, or they may log a response indicating that they decline the survey. Self-identification data is important to the University’s ability to accurately identify barriers to inclusion and to develop strategies to eliminate these barriers. Any information directly related to you is confidential and cannot be accessed by the reviewers or the Medicine by Design team. Aggregated results as of the closing of this posting may be shared with only a small number of designated senior administrators on a need-to-know basis.

How to Apply

To apply for Phase 1 funding, please download the following documents, complete them and submit them according to the instructions in each. Please note that all applicants (lead and co-PIs) are required to answer the self-identification survey.

Looking for a team?

A goal of Medicine by Design’s Grand Questions Program is to facilitate new connections within the broader research community. If you are an investigator who is interested in joining a team or is interested in adding additional team members, please fill out this form by July 31, 2020. Medicine by Design will circulate a list of all investigators interested in working on each Grand Question.