Web address:
http://www.sciencedaily.com/releases/2011/01/
110106145311.htm
Scientists Construct Synthetic Proteins That Sustain Life
enlarge
Michael Hecht, a professor of chemistry at Princeton University, has led a team
of researchers who have for the first time constructed artificial proteins that
enable the growth of living cells. The synthetic proteins were designed from
scratch and expressed from artificial genes. He is holding samples of living
bacteria containing the synthetic proteins. (Credit: Photo by Brian Wilson)
ScienceDaily (Jan. 7, 2011) In a groundbreaking achievement that could help
scientists "build" new biological systems, Princeton University scientists have
constructed for the first time artificial proteins that enable the growth of
living cells.
The team of researchers created genetic sequences never before seen in nature,
and the scientists showed that they can produce substances that sustain life in
cells almost as readily as proteins produced by nature's own toolkit.
"What we have here are molecular machines that function quite well within a
living organism even though they were designed from scratch and expressed from
artificial genes," said Michael Hecht, a professor of chemistry at Princeton,
who led the research. "This tells us that the molecular parts kit for life need
not be limited to parts -- genes and proteins -- that already exist in nature."
The work, Hecht said, represents a significant advance in synthetic biology, an
emerging area of research in which scientists work to design and fabricate
biological components and systems that do not already exist in the natural
world. One of the field's goals is to develop an entirely artificial genome
composed of unique patterns of chemicals.
"Our work suggests," Hecht said, "that the construction of artificial genomes
capable of sustaining cell life may be within reach."
Nearly all previous work in synthetic biology has focused on reorganizing parts
drawn from natural organisms. In contrast, Hecht said, the results described by
the team show that biological functions can be provided by macromolecules that
were not borrowed from nature, but designed in the laboratory.
Although scientists have shown previously that proteins can be designed to fold
and, in some cases, catalyze reactions, the Princeton team's work represents a
new frontier in creating these synthetic proteins.
The research, which Hecht conducted with three former Princeton students and a
former postdoctoral fellow, is described in the online journal PLoS ONE,
published by the Public Library of Science.
Hecht and the students in his lab study the relationship between biological
processes on the molecular scale and processes at work on a larger magnitude.
For example, he is studying how the errant folding of proteins in the brain can
lead to Alzheimer's disease, and is involved in a search for compounds to
thwart that process. In work that relates to the new paper, Hecht and his
students also are interested in learning what processes drive the routine
folding of proteins on a basic level -- as proteins need to fold in order to
function -- and why certain key sequences have evolved to be central to
existence.
Proteins are the workhorses of organisms, produced from instructions encoded
into cellular DNA. The identity of any given protein is dictated by a unique
sequence of 20 chemicals known as amino acids. If the different amino acids can
be viewed as letters of an alphabet, each protein sequence constitutes its own
unique "sentence."
And, if a protein is 100 amino acids long (most proteins are even longer),
there are an astronomically large number of possibilities of different protein
sequences, Hecht said. At the heart of his team's research was to question how
there are only about 100,000 different proteins produced in the human body,
when there is a potential for so many more. They wondered, are these particular
proteins somehow special? Or might others work equally well, even though
evolution has not yet had a chance to sample them?
Hecht and his research group set about to create artificial proteins encoded by
genetic sequences not seen in nature. They produced about 1 million amino acid
sequences that were designed to fold into stable three-dimensional structures.
"What I believe is most intriguing about our work is that the information
encoded in these artificial genes is completely novel -- it does not come from,
nor is it significantly related to, information encoded by natural genes, and
yet the end result is a living, functional microbe," said Michael Fisher, a
co-author of the paper who earned his Ph.D. at Princeton in 2010 and is now a
postdoctoral fellow at the University of California-Berkeley. "It is perhaps
analogous to taking a sentence, coming up with brand new words, testing if any
of our new words can take the place of any of the original words in the
sentence, and finding that in some cases, the sentence retains virtually the
same meaning while incorporating brand new words."
Once the team had created this new library of artificial proteins, they
inserted those proteins into various mutant strains of bacteria in which
certain natural genes previously had been deleted. The deleted natural genes
are required for survival under a given set of conditions, including a limited
food supply. Under these harsh conditions, the mutant strains of bacteria died
-- unless they acquired a life-sustaining novel protein from Hecht's
collection. This was significant because formation of a bacterial colony under
these selective conditions could occur only if a protein in the collection had
the capacity to sustain the growth of living cells.
In a series of experiments exploring the role of differing proteins, the
scientists showed that several different strains of bacteria that should have
died were rescued by novel proteins designed in the laboratory. "These
artificial proteins bear no relation to any known biological sequences, yet
they sustained life," Hecht said.
Added Kara McKinley, also a co-author and a 2010 Princeton graduate who is now
a Ph.D. student at the Massachusetts Institute of Technology: "This is an
exciting result, because it shows that unnatural proteins can sustain a natural
system, and that such proteins can be found at relatively high frequency in a
library designed only for structure."
In addition to Hecht, Fisher and McKinley, other authors on the paper include
Luke Bradley, a former postdoctoral fellow in Hecht's lab who is now an
assistant professor at the University of Kentucky, and Sara Viola, a 2008
Princeton graduate who is now a medical student at Columbia University.
The research was funded by the National Science Foundation.
Email or share this story:
| More
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily
staff) from materials provided by Princeton University. The original article
was written by Kitta MacPherson.
Journal Reference:
1. Mark Isalan, Michael A. Fisher, Kara L. McKinley, Luke H. Bradley, Sara
R. Viola, Michael H. Hecht. De Novo Designed Proteins from a Library of
Artificial Sequences Function in Escherichia Coli and Enable Cell Growth. PLoS
ONE, 2011; 6 (1): e15364 DOI: 10.1371/journal.pone.0015364
Need to cite this story in your essay, paper, or report? Use one of the
following formats:
APA
MLA
Princeton University (2011, January 7). Scientists construct synthetic proteins
that sustain life. ScienceDaily. Retrieved January 8, 2011, from
http://www.sciencedaily.com /releases/2011/01/110106145311.htm
Note: If no author is given, the source is cited instead.
Disclaimer: Views expressed in this article do not necessarily reflect those of
ScienceDaily or its staff.
------------------------------------
Post message: [email protected]
Subscribe : [email protected]
Unsubscribe : [email protected]
List owner : [email protected]
Homepage : http://proletar.8m.com/Yahoo! Groups Links
<*> To visit your group on the web, go to:
http://groups.yahoo.com/group/proletar/
<*> Your email settings:
Individual Email | Traditional
<*> To change settings online go to:
http://groups.yahoo.com/group/proletar/join
(Yahoo! ID required)
<*> To change settings via email:
[email protected]
[email protected]
<*> To unsubscribe from this group, send an email to:
[email protected]
<*> Your use of Yahoo! Groups is subject to:
http://docs.yahoo.com/info/terms/
