[tt] de novo ribosome

[Eugen Leitl]

http://www.bloomberg.com/apps/news?pid=20601124&sid=aWNwdtOMONZ8&refer=home 

Harvard Scientists’ Discovery Opens Door to Synthetic Life

By John Lauerman

March 7 (Bloomberg) -- Harvard University scientists are a step closer to
creating synthetic forms of life, part of a drive to design man-made
organisms that may one day be used to help produce new fuels and create
biotechnology drugs.

Researchers led by George Church, whose findings helped spur the U.S. human
genome project in the 1980s, have copied the part of a living cell that makes
proteins, the building blocks of life. The finding overcomes a major
roadblock in making synthetic self-replicating organisms, Church said today
in a lecture at Harvard in Cambridge, Massachusetts.

The technology can be used to program cells to make virtually any protein,
even some that don’t exist in nature, the scientists said. That may allow
production of helpful new drugs, chemicals and organisms, including living
bacteria. It also opens the door to ethical concerns about creation of
processes that may be uncontrollable by life’s natural defenses.

“It’s the key component to making synthetic life,” Church said yesterday in a
telephone call with reporters. “We haven’t made synthetic life and it’s not
our primary goal, but this is a huge milestone in that direction.”

The work may be immediately helpful to companies such as Synthetic Genomics
Inc., headed by J. Craig Venter, trying to make new organisms that perform
specific tasks, such as converting buried coal into methane gas that’s easier
to extract from the ground.

Microbes for Coal

Venter’s plan is to create man-made microbes that can help break down the
coal in the earth, much as bacteria speed decomposing plant material.

In a conference for alumni today at Harvard, Church described how his team
assembled a reconstituted ribosome, the first artificial version of the
structure capable of remaking itself.

Naturally occurring ribosomes are used now when biotechnology companies
genetically engineer cells to make the proteins for vaccines and drugs, such
as Genentech Inc.’s Herceptin. Normal ribosomes make some drugs slowly, and
others can’t be made at all, said Anthony Forster, a Vanderbilt University
pharmacologist who has collaborated with Church on synthetic biology
projects.

A man-made, or reconstituted, ribosome may be programmable to make all kinds
of molecules, Forster said.

Efficient Protein Making

“There would be advantages to having ribosomes that would only make specific
proteins” said James Collins, a Boston University biomedical engineer, in a
telephone interview. “Then you could program ribosomes so that they shut down
much of the rest of the cell, only making the proteins you want to produce.
You could shift the cell’s machinery to making certain products or fuels, for
example, and really increase efficiency.”

Specially programmed ribosomes might also have the ability to make mirror
images of the active molecules in existing drugs, Church said. These
mirror-image versions, sometimes called chirals, would be impervious to
enzymes that the body usually uses to break down chemicals.

“They would have a longer stability in natural environments,” Church said.

Ribosomes have been synthesized before, some as long as 40 years ago. Because
they were made only under specialized conditions of temperature and salt
concentration, scientists couldn’t get them to recreate themselves, a key
requirement in making artificial life.

Security Concerns

Artificial life and drugs that can’t be broken down by the body’s natural
enzymes raise a number of serious concerns, said David Magnus, director of
the Stanford Center for Biomedical Ethics.

As the tools of synthetic biology become easier to use, bioterrorists and
criminals may attempt to exploit them, he said. Well-meaning scientists might
also release potentially deadly organisms and chemicals into the environment.

“A number of proposals have been made about controlling access to this
technology,” Magnus said in a telephone interview. “The synthetic biology
community takes these issues seriously and are talking about what it will
take to make sure we have effective oversight.”

The first artificial organisms are likely to be grown in highly controlled
conditions, and would probably be unable to exist outside the laboratory,
said Vanderbilt’s Forster.

Lab Escape Improbable

“It might sound scary initially, but it would almost be on life support,” he
said. “It would probably be highly dependent on someone feeding it 30 or more
small molecules. It wouldn’t be likely to escape into the environment and run
amok.”

Church has advised 22 companies on genetic sequencing since 1984. Technology
he developed was licensed to Applied Biosystems Inc., purchased last year by
Life Technologies Corp. The technology is used to make Life’s sequencing
products.

The Harvard geneticist last year received backing from Google Inc. for a
project to decipher the genomes of 100,000 people using sequencers, machines
that quickly read the genetic code, the instructions for making all its
proteins that is stored in DNA molecules. A complementary molecule, called
RNA, sends the genetic messages to structures called ribosomes that act like
factories producing proteins.

New Help

To reach his latest goal, Church last year hired Michael Jewett, a chemical
and biological engineer who had been at Stanford University near Palo Alto,
California. Jewett was one of the few people who had the knowledge of protein
synthesis to move the effort forward. The project was done within a year.

“We really thought this was going to be hard, I can’t overemphasize that,”
Church said. “I’m probably not articulating how exciting this is.”

Jewett quickly found ways to make and assemble the 54 proteins and three RNA
molecules that go into making a ribosome. Church said he now has a “tubeful”
of reconstituted ribosomes, containing millions of the artificial structures.
While the findings haven’t been published, Church said they’ve been
replicated many times.

Church “is a pioneer in biotechnology who, with this latest study, has
established himself as a pioneer in synthetic biology,” said Boston
University’s Collins.

To contact the reporter on this story: John Lauerman in Boston at
jlauerman at bloomberg.net.

Last Updated: March 7, 2009 16:00 EST