Cisbio eBook - 30

Trends in Protein-Protein Interactions Research | Life's Code Accepts New Characters

So far, the scientists have synthesized 6.5 of the
yeast's 16 chromosomes, and they are working
on creating the remaining ones. Once all 16
chromosomes are ready, the researchers will integrate them into a single cell. By doing so, "we're
changing what is known to nature," Dr. Mitchell
emphasized, "and testing the rules of genetics to
see if what we understand is actually true."

Testing New Codes
Genomically recoded organisms (GROs) is a term
of art used to designate E. coli and yeast that
contain altered genetic codes, noted Dr. Carr.
Several years ago, he worked on the initial stages
of a project alongside Dr. Church and others to
free up one of E. coli's codons.
Although he is no longer directly involved in the
project, which is currently focused on freeing up
more of the bacterium's codons, Dr. Carr said that
he has been using what he learned for new work
on designing effective genetic codes that don't
take 10 years of experiments to get right.
Instead, he and colleagues are working to predict,
30 | GENengnews.com

computationally, what codes will be successful,
then testing the protein synthesis of those in test
tubes. The team corrects code mistakes back on
the computer and then retests corrected codes in
test tubes in a reiterative process, over and over,
until a code is ready to be tried in a cell.
This design process is important, Dr. Carr
explained, as researchers strive to build genetic
codes that live up to all of the promising opportunities of synthetic biology. Among Dr. Carr's
favorites: Engineering resistance to viral infection
into cells, while producing "genetic firewalls" to
block the flow of genes to and from these organisms. For this to happen, the genetic code of an
organism must be altered to allow it to live, but
different enough from a virus or bacterium to
prevent them and their infiltrating genetic material from being translated into proteins in the
host.
The language must be different even though
the blueprint remains the same, Dr. Carr insisted.
How different is different enough? No one knows
yet, but it's something Dr. Carr and others want

to figure out. If they succeed, agricultural animal
cells could be recoded to stop the spread of
disease. Human cells could be rewritten, too.
They could be engineered so that a virus would
never infect them again.
"It is a long road," concluded Dr. Carr, "but there
are some amazing opportunities ahead." n

References
1. Zhang Y, et al. A semi-synthetic organism that stores and
retrieves increased genetic information. Nature 2017.
November; 551: 644-647. doi:10.1038/nature24659.
2. Italia JS, et al. An orthogonalized platform for genetic
code expansion in both bacteria and eukaryotes. Nat.
Chem. Biol. 2017 Apr; 13(4): 446-450. doi: 10.1038/
nchembio.2312.



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