[ExI] Harvard scientists create cell protein machinery

[Rick Strongitharm]

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http://www.harvardscience.harvard.edu/foundations/articles/taking-a-stride-toward-synthetic-life
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*Harvard scientists create cell protein machinery*

*March 7, 2009*

*Alvin Powell
Harvard News Office*

Harvard scientists have cleared a key hurdle in the creation of synthetic
life, assembling a cell’s critical protein-making machinery in an advance
with both practical, industrial applications and that advances the basic
understanding of life’s workings.

George Church<http://www.harvardscience.harvard.edu/directory/researchers/george-church>,
a genetics professor at Harvard Medical School
<http://www.hms.harvard.edu/>and member of Harvard’s Origins
of Life Initiative<http://www.harvardscience.harvard.edu/directory/programs/origins-life-initiative>,
reported the creation of billions of synthetic
ribosomes<http://cellbio.utmb.edu/CELLBIO/ribosome.htm>that readily
create a long, complex protein called firefly luciferase.

Church, speaking at a Harvard Alumni Association and Origins of Life
Initiative event at the Science Center on Saturday afternoon (March 7),
described the advance for the first time publicly as part of an afternoon
symposium called “The Future of Life.”

“We have not made artificial
life<http://www.pbs.org/wgbh/nova/sciencenow/3214/01.html>,
and that is not our primary goal, but this is a huge milestone in that
direction,” Church said in comments on the work before the event.

Ribosomes are bodies inside of each cell that take the instructions
from DNA<http://www.dnaftb.org/15/concept/>and use them to create the
proteins encoded by specific genes. Proteins are
critical to forming the body’s structure, including muscles, bones and
tendons, and are also critical in its daily functioning, through enzymes,
for example, which control metabolism.

“The reason it is a step toward artificial life is that the key component of
all living systems is the ribosome, which does protein synthesis. It is the
most conserved and one of the most complicated biological machines,” Church
said.

Using the bacteria E.
coli<http://www.cdc.gov/nczved/dfbmd/disease_listing/stec_gi.html#1>,
Church and Research Fellow Michael Jewett
<http://www.harvardscience.harvard.edu/directory/researchers/michael-jewett>extracted
the bacteria’s natural ribosomes, broke them down into their constituent
parts, removed the key ribosomal RNA and then synthesized the
ribosomal RNA<http://nobelprize.org/educational_games/medicine/dna/>anew
from molecules.

Though the advance may create excitement among researchers interested in
life’s basic functioning, Church said that the work’s industrial
applications were its driving force.

Industry today manufactures proteins on a large scale using natural
ribosomes, which evolved over millions of years for natural, not industrial,
reasons. Church said that being able to create a ribosome means also being
able to tweak it so it better fits industrial needs. One possible use would
be to create mirror-image proteins that would be less susceptible to
breakdown by enzymes, making them longer-lived.

“You really are in control. It’s like the hood is off and you can tinker
directly,” Church said.

The advance breaks a 40-year period with little progress in artificial
ribosome creation, Church said. The last significant work in this area was
done in 1968, when researchers assembled an artificial ribosome, but in an
unusual chemical environment rather than an environment in which protein
synthesis normally occurs, as Church and Jewett did.

Church and Jewett expected creating the artificial ribosome and getting it
to produce proteins would be the toughest steps in making an artificial
cell. They were amazed, Church said, when the task was accomplished in just
a year.

The ultimate goal is to create an artificial genome of 151 genes that they
believe are the minimum to create a functioning, self-replicating cell.

“It could be that the hardest steps are still ahead of us,” Church said.

Joining Church at Saturday’s event were human genome pioneer and visiting
scholar Craig Venter<http://www.harvardscience.harvard.edu/foundations/articles/j-craig-venter-named-visiting-scholar>;
Jack Szostak<http://www.harvardscience.harvard.edu/directory/researchers/jack-szostak>,
professor of genetics at Harvard Medical School and Massachusetts General
Hospital<http://www.harvardscience.harvard.edu/directory/programs/massachusetts-general-hospital>;
George Whitesides<http://www.harvardscience.harvard.edu/directory/researchers/george-whitesides>,
Woodford L. and Ann A. Flowers Professor of Chemistry and Chemical
Biology<http://harvardscience.harvard.edu/directory/programs/department-chemistry-and-chemical-biology>;
and Andrew Knoll<http://www.harvardscience.harvard.edu/directory/researchers/andrew-knoll>,
Fisher Professor of Natural History and professor of Earth and Planetary
Sciences<http://harvardscience.harvard.edu/directory/programs/department-earth-and-planetary-sciences>.
Harvard Provost Steven E.
Hyman<http://www.harvardscience.harvard.edu/directory/researchers/steven-e-hyman>introduced
the event. It was moderated by professor of
astronomy<http://harvardscience.harvard.edu/directory/programs/department-astronomy>and
Origins of Life Director Dimitar
Sasselov<http://www.harvardscience.harvard.edu/directory/researchers/dimitar-sasselov>
.

Szostak presented his recent research into the creation and propagation of
synthetic cells, showing that membranes form from simple fat molecules
spontaneously under certain conditions. In addition to the membranes, he
reviewed research into possible ways that basic genetic information may have
originally been stored and conveyed in simple RNA-like molecules. His work,
he said, is exploring the properties of these RNA-like molecules, seeking
variations that make them better early candidates to store and replicate
genetic information than either DNA or RNA, which perform those functions in
modern cells, but require complex molecular machinery to do so.

In his presentation, Venter described the search for genes around the world,
saying that microbes have been found on earth that can withstand radiation
levels far beyond that which would be lethal to humans, that can live in
corrosive liquids that would eat away a human finger dipped in it, and in a
wide array of other environments.  The growing library of genes from
creatures of all kinds – totaling 50,000 gene families – has created a
database from which industry can pick and choose genes for particular
applications. Using genetic engineering, synthetic genomes can be created to
do such useful things as create clean-burning synthetic fuels, he said.

“I think we’re limited primarily by our own imagination,” Venter said.


-- 
"Dogma blinds."
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