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The First Genome Project Write (GP-Write) Canada Meeting

 Dr. Bogumil Karas (Western University) showing that many organisms can contribute to GP-Write.

Dr. Bogumil Karas (Western University) showing that many organisms can contribute to GP-Write.

The first Genome Project Write (GP-Write) Canada meeting was hosted in Montréal on August 13-14th 2018, organized by Dr. Vincent Martin (Concordia University), and Dr. Bogumil Karas (Western University). GP-Write is an international consortium of researchers with the ultimate goal of creating a synthetic human genome. GP-Write is a continuation of the Human Genome Project (HGP) which, from 1990 to 2003, produced the sequence of the complete human genome. The effort of the International Human Genome Sequencing Consortium significantly reduced the costs of DNA sequencing by developing new technologies and making it more accessible. Today, reading genomes has become an established technique. Now, we are entering an era that goes beyond reading genomes. It is about writing (or creating) them. In fact the first bacterial genome was synthesized in 2010 at the J.Craig Venter Institute and the first synthetic yeast genome (Synthetic Yeast 2.0) is currently under development.

However, writing genomes continues to be challenging, and many more hurdles must be overcome to move from bacteria and yeast to human genomes. One of the major bottlenecks is the difficulty of DNA synthesis itself, in addition to the assembly, delivery, installation, and editing of synthetic genomes.

But why do we want to synthesize human genomes at all? Creating the whole or parts of the human genome will advance our understanding of how genomic elements function as a system. Or as Richard Feynman put it, "What I cannot create, I do not understand". This will allow us to study gene interactions to model diseases and to develop new drugs. And it will largely facilitate the development of advanced gene- and cell-based therapeutics for the treatment of currently incurable diseases.

GP-write has already held two international scientific working meetings where leading Canadian scientists, including Bogumil Karas, Vincent Martin, Peter Zandstra and others, have expressed their interest becoming part of it. Thus, the objective of the GP-write Canada meeting was to determine who else in Canada is interested to build a GP-write Canadian consortium, which Canadian resources and scientific expertise can be leveraged, and which potential projects and strategies will attract funding to synthetic genomics research in Canada. The event attracted more than 70 participants from across the country, including scientists, industry leaders, and ethicists who introduced their work and discussed related questions over the course of two days.

Biology is the most sophisticated manufacturing technology on the planet: self-repairing, self-assembling, self-replicating, renewable, resilient.
— Dr. Kevin Madden

Day 1

The workshop started with an afternoon of inspirational talks by industrial and academic leaders in the field, covering the past, the present, and the future of genome writing.

  • Dr. Andrew Hessel inspired us with a short personal and scientific story that covered the early days of DNA sequencing, the first “synthetic” bacterium, and a future world when synthesizing human genomes may become mainstream.

  • Dr. Bogumil Karas proposed that synthetic biologists specialized in different host organisms tackle various stages of the synthetic genome engineering cycle including design, DNA synthesis, assembly, delivery, and editing. Bogumil gave a comprehensive technical road-map on many of the challenges that have to be overcome in these various stages. He also suggested that cell fusion could be used to deliver large chromosomes into plant cells.

  • Dr. Leslie Mitchell (Boeke lab) talked about current progress and challenges of the Synthetic Yeast 2.0 project that aims to build the world’s first synthetic eukaryotic genome. She also shared her recent work in transplanting and analyzing synthetic genomic loci in mouse embryonic stem cells.

  • Dr. Kevin Madden presented on Ginkgo Bioworks foundries that allow the undertaking of several projects in parallel by automating synthetic biology using advanced robotics.

  • Samir Hamadache (Western University) highlighted the need of accelerator programs dedicated to synthetic genomics, so Canada can emerge as a leader in the industry.

You don’t need to work in human cells to contribute to GP-write Canada.
— Dr. Bogumil Karas

Day 2

The second day started with a series of talks by researchers from various Canadian universities to elaborate what research is currently in progress in Canada and how it can contribute to the GP-Write Canadian consortium.

 Dr. Miodrag Grbic (Western University) brings back the importance of good quality genomic data.

Dr. Miodrag Grbic (Western University) brings back the importance of good quality genomic data.

  • Dr. Aashiq Kachroo (Concordia University) is working on humanized yeast by swapping multiple yeast genes with their human versions for drug-screening or to assay genetic diseases.

  • Dr. Sebastian Rodrigue (Université de Sherbrooke) showed that his team successfully cloned the entire genome of Mesoplasma florum into yeast and they are working on new techniques for genome assembly and transplantation into microorganisms.

  • Dr. Scott McComb (National Research Council) is using CRISPR-deletion techniques to make multiple knockouts simultaneously and map pathways in human T cells. He suggested to use human T cells as chassis for developing, integrating and studying synthetic genes and genomes.

  • The importance of the ethics and of good communications to the public in the GP-Write project was highlighted by Dr. Marc Saner from the University of Ottawa.

  • Dr. Teodore Veres (National Research Council) is working to scale down wet lab workflows with automation and precision using lab-on-a-chip and microfluidic technologies.

  • Dr. Michael Tyres (University of Montreal) talked about his work on CRISPR/Cas9 genetic screens in human cells and on engineering yeast strains that produce defined small molecules to modify the human microbiome.

  • Dr. Steve Hallam’s team from the University of British Columbia is working on automated high-throughput screening platform for enzymes function discovery.

  • Dr. Laura Prochazka (University of Toronto) is engineering gene circuits to manipulate the decision-making of human stem cells and proposed human pluripotent stem cells as a chassis to analyze and study the synthetic chromosome.

  • A good quality genome needs good sequencing techniques as reminded by Dr. Trevor Charles (University of Waterloo). He also highlighted current gene editing work in agriculture and greenhouse technology and how GP-write can contribute in these fields.

  • Dr. Charles Boone (University of Toronto) created a genetic interaction map of the yeast genome and functionally annotated each gene. He highlighted that automation of the process of creating multi-genic knockouts is required to accelerate the establishment of such a genetic interaction maps.

  • Dr. Miodrag Grbic (Western University) is studying the genomics of spider mites and he is proposing that the small genome of this eukaryote could be synthesized as a proof of concept before going directly to the human chromosome.

 Like Dr. Sebastian Rodrigue (Université de Sherbrooke) and his team, Canadian researchers have multiple expertise that can be integrated to a Canadian consortium.

Like Dr. Sebastian Rodrigue (Université de Sherbrooke) and his team, Canadian researchers have multiple expertise that can be integrated to a Canadian consortium.

The afternoon of Day 2 was broken into two focused breakout sessions. In small working groups, we first discussed Canada’s unique opportunities and challenges with respect to GP-Write. For the second breakout session, groups were organized based on their expertise and/or interest in various taxa of host organisms. Participants discussed ways in which Canadian expertise with different hosts can contribute to a unified GP-Write strategy.

The notes generated by the discussions were compiled by George Brook from the Agricola Group and Vincent Martin, who will produce a report on the conference’s outcomes. This document will then be used to lobby for funding agencies.

We have learned a lot of exciting work and ideas throughout this workshop and had fruitful discussions with an enthusiastic and diverse group of people, showcasing that Canada could become an important actor in the GP-Write worldwide consortium.

Andrew Diamond