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Synthetic Biology at the University of Toronto: Medicine by Design and Beyond

Laura Prochazka - October 28, 2019

Medicine is entering a new era where chemicals will be replaced with engineered cells that perform human defined functions; where transplants from human donors will be replaced with de novo (in the laboratory) engineered tissues and organs; where damaged tissues and organs will be regenerated inside our body; where diagnostics will detect diseased states prior to appearance of symptoms; and where our genome is edited to prevent incurable genetic diseases. Medicines are going to be precise, safe, preventative and curative. Medicines are going to be made by design and synthetic biology is going to be a key enabler to realize these new approaches in medicine.

Figure 1: Medicine by Design banner. Photo credit: Neil Ta

Figure 1: Medicine by Design banner. Photo credit: Neil Ta

Medicine by Design Invests in Synthetic Biology 

Figure 2: (a) Attendees of the MbD Synthetic Biology Discussion Group and (b) how they define / think about synthetic biology

Figure 2: (a) Attendees of the MbD Synthetic Biology Discussion Group and (b) how they define / think about synthetic biology

Medicine by Design is not only a promising concept; it is also the name of an initiative at the University of Toronto (U of T) that aims to accelerate this new era of medicine. Medicine by Design is funding early-stage and translational projects in primarily regenerative medicine. It also sponsors post-doctoral fellowships and travel awards, offers communication-, career- and commercialization workshops, and much more. Importantly, the initiative also invests in synthetic biology. For example, it helped launch the Medicine by Design Synthetic Biology Discussion Group, which takes place once per month alongside the Single Cell, Organoid and Computational Discussion Group meetings. The Medicine by Design Synthetic Biology Discussion Group has more than 140 subscribers, including students, post-doctoral fellows and professors at U of T, as well as professionals from industry and government (Figure 2). The event offers a space to present work, discuss synthetic biology-related topics, start collaborations and, not to forget, enjoy Medicine by Design sponsored pizza. For more information, please see below the summary of past discussion group meetings. It gives a good overview of synthetic biology-related work that is currently happening at U of T.

Other efforts include bringing synthetic biology closer to high-school students with booths at the Regenerative Medicine Expo or financial support of the U of T’s iGEM team. Medicine by Design has also supported the hiring of several new faculty members with expertise in synthetic biology, including Prof. Keith Pardee in the Leslie Dan Faculty of Pharmacy (cell-free synthetic biology), and Prof. Leo Chou (DNA nanotechnology) and Prof. Michael Garton (mammalian synthetic biology) at the Institute of Biomaterials & Biomedical Engineering. Finally, Medicine  by Design is funding interdisciplinary projects that integrate the expertise of those new faculty and more senior synthetic biology faculty, including Prof. Krishna Mahadevan (Metabolic Systems Engineering).

A short summary of previous and future MbD Synthetic Biology Discussion Group meetings:

2018 

February 28th Dr. Benjamin Scott, former PhD student Belinda Chang lab, current postdoctoral associate at the National Institute of Standards and Technology (NIST) in Washington DC “Studies of Human GPCRs Using Yeast” & “The Goals of SynBio Canada”

March 27th Dr. Trevor McKee, Group leader at the Computational Pathology core facility at STARR “Moving from Images to Data: Resources and expertise in computational pathology at the STTARR core facility”

April 24th Dr. Brendan Hussey, former PhD student David McMillen lab, current postdoc “Programmable T7-based synthetic transcription factors”

June 26th Aaron Trotman-Grant (MSc Student Dana Philpott lab) & Laura Prochazka (Postdoc Peter Zandstra lab) “Trends in Mammalian Synbio: Take home massages from the 5th International Mammalian Synbio Conference”

July 31th Ashton Trotman-Grant, PhD student Juan Carlos Zuñika-Pflücker lab “Designing ‘Smart’ Immune Cells to Expand Therapeutic Capabilities”

August 28th Christian Euler, PhD student Krishna Mahadevan lab “Reverse and Forward Engineering: Modeling Real and Synthetic Systems”

October 30th Kaushik Raj, PhD student Krishna Mahadevan lab “Emergent properties in gene regulation”

Figure 3: Self-identification and interest in synthetic biology among the participants of the MbD Synthetic Biology Discussion Group

Figure 3: Self-identification and interest in synthetic biology among the participants of the MbD Synthetic Biology Discussion Group

November 27th Dr. Keith Pardee, Assistant Professor at Leslie Dan Pharmacy Faculty “Rapid, Low-cost Tools for Human Health”

2019

March 26th Dr. Leo Chou, Assistant Professor Institute of Biomaterials and Biomedical Engineering (IBBME) “What can DNA nanotechnology do for synthetic biology”

April 30th Lyla El-Fayomi, MSc student Derek van der Kooy labScience at the Speed of Light: Optogenetics 101”

May 28th Dr. Michael Garton, Assistant Professor Institute of Biomaterials and Biomedical Engineering (IBBME) “Bringing protein interface design to the synthetic biology party”

July30th Jenise Chen (PhD Student Shana Kelley lab)“A multiplexed, electrochemical interface for cell-free synthetic toehold-mediated gene networks”

October 29th Dr. Michael Aregger (Postdoc Moffat lab) “Global mapping of human genetic interactions using CRISPR-Cas screens”

More Synthetic Biology at the University of Toronto

Medicine by Designs’ investment in synthetic biology has been great, but medicine is certainly not the only application where the field is going to make a difference. In fact, U of T  has been in the synthetic biology game long before Medicine by Design existed. For example, the centre for Applied Bioscience and Engineering (BioZone) at U of T was created to promote work at the interface of biology and engineering. BioZone is integrating expertise in computational modeling, genomics, enzyme-, metabolic- and process engineering with a focus on production of biofuels, bioremediation, wastewater treatment, and microbiome-related health applications. There is also the Synthetic Biology Innovation Cluster founded in 2013 by U of Ts’ Impact Centre, led by Prof. David McMillen and Stanley Wong. The cluster aims to connect industry and academics in Ontario and has hosted several successful summer programs to help train the next generation of synthetic biologists. Importantly, U of Ts’ innovative research in synthetic biology combined with Toronto’s start-up scene has already led to the creation of synbio startups including Phycus Biotechnologies, Spindle Biotech, and Ranomics.

U of T is also a leading institution in genomics, systems biology and artificial intelligence, which are areas that are certainly becoming more integrated with synthetic biology. Examples are the laboratories of Prof. Alán Aspuru-Guzik (AI, lab automation, material & drug discovery), Prof. Brendan Frey (AI, Systems Genomics) with company DeepGenomics, Prof. Charles Boone & Prof. Tim Hughes (functional genomics), and Prof. Jason Moffat (genome editing, systems biology). (and yes, the list could go on and on, so please forgive me for stopping here, missing many other excellent labs.)

Finally, U of T has a highly active and well organized iGEM team that has operated since 2007, and with every year the number of interested students and their success at the international iGEM competition increases. Last but not least, let’s not forget the numerous proactive U of T students who, despite the lack of formal synbio programs and, until now, sparse numbers of synbio laboratories, follow their passion and conduct synbio related projects in non-synbio labs, engage in the Medicine by Design discussion group meetings and help create a U of T and Canadian synthetic biology community (highlighting U of T alumni, Dr. Benjamin Scott who created synbiocanada.org).

Opportunity Biology by Design

With that I want to close, and hope that this post was somewhat useful, in particular for current and future students and postdocs at U of T who aim to pursue a career in synthetic biology, for those who feel a little lost in the giant U of T system and for those who are looking for a program and appropriate training in synthetic biology.  As a side note, the number of students in the latter category is probably larger than we think. This is supported by the fact that U of Ts’ iGEM team had more than 200 applicants last year, and by the number of students who indicated that they are interested in synthetic biology but don’t conduct work in the area on the synthetic biology discussion group survey (Figure 3).

Certainly, dedicated programs and funding are very much needed but until then, I believe, there are numerous ways to work in, transition to or engage in synthetic biology at U of T. In the end, synthetic biology is just a term. Synthetic biology is molecular biology, computational biology, systems biology, cell biology, genetics, engineering, creativity, design, ideas, dedication…. it is the learning of how to create biological devices and systems so we can make medicines by design, agriculture by design, food by design, remediation by design, energy by design. So we can make biology by design. So we can eventually make everything (well almost) of biology! Thus, regardless of your department, lab or program, you can always create your own “synbio mind” and sooner or later become part of the solutions that allow us to take care of our health and the environment. I am convinced there are plentiful ways to do that at U of T and at any other institution in Canada.

Thanks for reading and please feel free to drop some comments below or send me or info@synbiocanada.org a message.

Acknowledgements

I want to thank Dr. Benjamin Scott (President of SynbioCanda.org) and Ann Perry (Manager, Strategic Communications & Operations at Medicine by Design) for proofreading and editing. Medicine by Design supports me with a Medicine by Design postdoctoral fellow award and is funded in part by a $114-million award from the Canada First Research Excellence Fund (CRFEF). I am further supported by CIHR. Finally, I want to thank Prof. Dr. Peter Zandstra for continuous support and mentorship.


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