---
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  family: Edmunds
  given: Scott
  url: https://orcid.org/0000-0001-6444-1436
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date: '2015-01-30T00:00:00+00:00'
date_updated: '2025-12-06T10:40:42+00:00'
guid: http://blogs.biomedcentral.com/gigablog/?p=1447
identifier: https://doi.org/10.59350/wfhj5-n6f24
image: http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/synYeastDiagram-1-300x175.jpg
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lang: en
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summary: '*The field of synthetic biology, designing and building engineered biological
  systems through DNA synthesis and genetic engineering, is rapidly moving to a genome
  scale. In a similar trajectory to genomic sequencing and genome projects two decades
  ago, it has moved from engineering single genes, entire synthetic bacterial genomes
  (J Craig Venter''s notorious "Synthia"), to the eukaryotic organism stage.'
title: 'Synthetic Genomics: Redesign and synthesis of the first multicellular eukaryotic
  genome'
url: https://wayback.archive-it.org/22098/2025-05-01T17:13:42Z/http://gigasciencejournal.com/blog/synthetic-genomics-redesign-and-synthesis-of-the-first-multicellular-eukaryotic-genome
version: v1
---

\*The field of [synthetic
biology](http://en.wikipedia.org/wiki/Synthetic_biology "Synthetic Biology"){target="_blank"
rel="noopener noreferrer"}, designing and building engineered biological
systems through DNA synthesis and genetic engineering, is rapidly moving
to a genome scale. In a similar trajectory to genomic sequencing and
genome projects two decades ago, it has moved from engineering single
genes, [entire synthetic bacterial
genomes](http://www.sciencemag.org/content/319/5867/1215) (J Craig
Venter\'s notorious
[\"Synthia\"](http://www.etcgroup.org/content/story-synthia)), to the
eukaryotic organism stage. The
[\"Sc2.0\"](http://syntheticyeast.org/sc2-0/ "Sc2.0 website"){target="_blank"
rel="noopener noreferrer"} synthetic yeast genome project, is an
[international
consortium](http://syntheticyeast.org/the-first-international-coordination-meeting-on-the-synthetic-yeast-project-to-propel-synthetic-biology-forward/)
synthesizing \"designer eukaryotic genomes\" for all of the 16
chromosomes (and roughly 14Mb of sequence) of Baker\'s yeast
Saccharomyces cerevisiae. With the first chromosome published last year
in Science, and many more already completed, and planning for the next
step up is already being discussed. Being heavily involved in Sc2.0, and
already producing several chromosomes (pictured), our colleagues at
[BGI](http://www.genomics.cn/en/index "BGI homepage"){target="_blank"
rel="noopener noreferrer"} organized a workshop covering this very topic
at the end of last year. Chantal Shen and Huanming Yang from BGI and
[Patrick Cai](http://www.cailab.org/ "Cai Lab"){target="_blank"
rel="noopener noreferrer"} from Edinburgh have written us a guest
posting on the discussions that went on at the workshop, and what the
proposed next steps are for organismal scale synthetic genomics.\
\*\
The first workshop to discuss and propose the international
collaboration on the projects in the field of synthetic genomics after
the Sc2.0 project was held on Sept. 12 in Shenzhen, China, as a part of
BGI\'s 9^th^ International Conference on Genomics (for a write up of
ICG9 [see](http://www.genomics.cn/en/news/show_news?nid=104155) this
report from BGI). The workshop was attended by the participants of the
Sc2.0 community from the USA, Europe, and China, as well as their
funding agencies.

![](http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/synYeastDiagram-1-300x175.jpg){.alignleft
.size-medium .wp-image-2104 loading="lazy" decoding="async"
srcset="http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/synYeastDiagram-1-300x175.jpg 300w, http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/synYeastDiagram-1-768x448.jpg 768w, http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/synYeastDiagram-1-1024x597.jpg 1024w, http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/synYeastDiagram-1.jpg 1318w"
sizes="(max-width: 300px) 100vw, 300px" width="300" height="175"}The
[publication on the synthesis of Chromosome
3](http://www.sciencemag.org/content/344/6179/55.full "Science Sc2.0 paper"){target="_blank"
rel="noopener noreferrer"} of the yeast genome on 28th March 2014
indicates the successful strategic roadmap and technical protocol of the
Sc2.0 project. Groups responsible for all other yeast chromosomes have
made good and smooth progresses. It is reasonable to be optimistic about
completion of all chromosomes ahead of schedule, even if the final
integration into a whole genome still remains a serious challenge. While
work is progressing rapidly, now is the right time to discuss what the
international participants of the Sc2.0 consortium should do next.

The workshop discussed two options in the coming years: 1) to synthesize
another more complicated monocellular genome with high throughput,
automated techniques, e.g. fission yeast or other higher fungus-like
mushrooms, to synthesize another monocellular eukaryotic organism with
the differentiation-like phenotypes, or to emphasize more on the
application to yeast breeding. The main argument for this approach was
to further encourage the positive responses from the public on synthetic
biology and anticipate further innovative technologies to further lower
the costs by integrated automation platforms; 2) to go directly to the
synthesis of the first multicellular eukaryotic genome.

The workshop reached the consensus that the next strategic mission for
the international consortium was to move towards the redesign and
synthesis of the first multicellular eukaryotic genome, while other
options as above, which should not be excluded, could be done by
individual labs. This was thought to be the most natural development
post-Sc2.0.

The workshop included seriously discussion and debate on the
technological challenges, emphasizing that the strategy of \"genome
replacement\" or homologous recombination might not be wholly applied to
multicellular organisms. The refined nuclear transfer technology for the
whole genome synthesis approach, and any other relevant emerging
technologies, such as CRISPR (see the [recent
review](https://doi.org/10.1186/2047-217X-3-24 "GigaScience review"){target="_blank"
rel="noopener noreferrer"} in *GigaScience*), should also be considered.
The collaborative approach with other communities, such as those in
biology, is essential. To be practical, the cost of synthesis, which is
approximately 10c per base now (one tenth of what it was at the
beginning of the Sc2.0), will need to further fall to one cent per base
in 5 years, or even lower.

The workshop also discussed and debated on the choice of the candidate
genome. The criteria for choice might be: 1) a smaller genome size; 2) a
well sequenced and annotated reference genome, 3) being well
characterized biologically and physiologically, 4) well established
culturing and phenotyping techniques.

[![DSC_0491](http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/DSC_0491-300x199.jpg){.size-medium
.wp-image-1449 .alignright loading="lazy" decoding="async"
srcset="http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/DSC_0491-300x199.jpg 300w, http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/DSC_0491-768x510.jpg 768w, http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/DSC_0491-1024x680.jpg 1024w"
sizes="(max-width: 300px) 100vw, 300px" width="300"
height="199"}](http://gigasciencejournal.com/blog/wp-content/uploads/2015/01/DSC_0491.jpg)\*\*The
road ahead: synthetic worms and beyond?\
\*\*As strongly suggested by [Sydney
Brenner](http://en.wikipedia.org/wiki/Sydney_Brenner "Sydney Brenner wikipedia"){target="_blank"
rel="noopener noreferrer"} (pictured visiting us at BGI) and his
colleagues in the nematode field, *C. elegans*, with a genome size
approximately 6 times larger than yeast (100Mb), and amongst the best
characterized model organisms in terms of its biology and development,
was considered as one of the strongest candidates, although other model
plant (e.g. *Arabidopsis*) or animal (e.g. *Drosophila*) genomes were
also looked at in the workshop. The differences among the different
candidates, both the advantages and disadvantages to our current
knowledge were compared. In addition to this, synthesizing an intact or
a part of a chromosome of a higher eukaryotic organism was also
proposed. The final choice will continue to be  to be debated before the
next meeting.

The workshop has proposed the general timetable for this
one-decade-initiative between 2015-2024: 2 years for discussion, 3 years
for pilot experiments, and 5 years for large-scale implementation. As
with the [Human Genome
Project](http://www.genome.gov/10001763 "NHGRI HGP timeline"){target="_blank"
rel="noopener noreferrer"}, the participants felt there was a high
likelihood of the project to be initiated and completed sooner than even
this speedy timeline due to the continuing rapid pace technological
breakthroughs, if managing to avoid any hesitations and delays. The
participants pledged their responsibility to carry the work out once the
tasks were assigned.

The workshop called for the broader international discussion about the
choice of the candidate genome, the strategy and details of the
technology, the roadmap, protocol and timetable of the initiative. Wider
participation and discussion from the various communities working on the
biology of the candidate organisms, and technical innovation and
development, was called for.

The principles of international collaboration and open data/tech-sharing
were again reaffirmed for the follow up project. As with China
participating in the Human Genome Project, groups from other developing
countries were encouraged to join and share this opportunity to
contribute to another milestone in the life sciences. However, the
facilities and capacities to guarantee its completion according to the
schedule would need to be evaluated.

The workshop also suggested the setting up of a coordination committee
and a 3B (bioethics, biosafety, and biosecurity) group to initiate the
relevant discussions. \"From scratch\" approaches and \"do-it-yourself\"
advocates were also considered. The participants also proposed the set
up of a \"SynBio Code\" for all the future members of the international
synbio community.

The next workshop or strategic meeting will be held in May 2015. The
meeting location is still to be decided but will be chosen in a
competitive way. Watch this space for further news on how these projects
are continuing.

**Huanming Yang**, Chairman, BGI Shenzhen\
**Patrick Cai**, Director, Edinburgh Genome Foundry\
**Chantal Shen**, Unit of Synthetic Biology, BGI Shenzhen

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