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July 12, 2007

Synthetic life projects

Venter's is trying to create a synthetic genome that will be housed within an existing bacterial cell, other scientists are aiming for the even more ambitious target of building an entire living cell from the basic chemical ingredients. However, George Church has a grander and I think more intersting vision.



George Church at Harvard Medical School in Boston, has devised a complete blueprint for a synthetic cell, an investment of around $10 million would be enough to turn the "bottom-up" dream into reality. "Our approach doesn't require any super new technology," he says.

In 2006 Church, working with Tony Forster of Vanderbilt University in Nashville, Tennessee, published a detailed blueprint for assembling a synthetic cell from scratch (Molecular Systems Biology, DOI: 10.1038/msb4100090). It includes 115 genes (133,000 base pairs)which would be combined with various biochemicals to make a self-assembling cell able to live under carefully controlled lab conditions. The details have still to be worked out, but Church believes there should be no fundamental barriers. He sees the team's artificial organism becoming a workhorse for biotechnology that could be adapted to do useful tasks such as making complex biochemicals.


How far can chemical self assembly be pushed ?
Self-assembly in vitro of viruses and the ribosome, achieved decades ago, taught us some of the principles assumed to be used in general by cells (Lewin, 2004). For example, self-assembly occurs in a definite sequence and is generally energetically favored, obviating the need for enzymes and an energy source. Assembling some type of cell (i.e. a self-replicating, membrane-encapsulated collection of biomolecules) would seem to be the next major step, yet detailed plans have not been published.

They have a stepwise biochemical approach that should lead to the eventual identification of any remaining functions essential for the synthesis of a minimal cell sustained solely by small molecules.



A minimal cell containing biological macromolecules and pathways proposed to be necessary and sufficient for replication from small molecule nutrients. The macromolecules are all nucleic acid and protein polymers and are encapsulated within a bilayer lipid vesicle. The small molecules (brown) diffuse across the bilayer. The macromolecules are ordered according to the pathways in which they are synthesized and act. They are colored by biochemical subsystem as follows: blue=DNA synthesis, red=RNA synthesis and cleavage, green=RNA modification, purple=ribosome assembly, orange=post-translational modification and black=protein synthesis. MFT=methionyl-tRNAfMeti formyltransferase. The system could be bootstrapped with DNA, RNA polymerase, ribosome, translation factors, tRNAs, MTF, synthetases, chaperones and small molecules.


All nucleoside modifications of all 33 synthetic tRNAs that may be sufficient for accurate translation
Murtas and his team have managed to initiate the process of protein synthesis in cell-like self-assembling spheres bounded by lipid membranes, known as "liposomes". A similar feat was achieved in 2004 by Vincent Noireaux and Albert Libchaber of Rockefeller University in New York, but while they seeded their lipid vesicles with an extract of Escherichia coli bacterial cells, Murtas and his colleagues used a recipe of 37 enzymes and a range of smaller molecules to enable protein synthesis.


So when are we likely to see unequivocally synthetic life, with the entire cell built from scratch? "It could be five months or 10 years," says Church. "These things aren't so much a question of timescales as the amount of money available."

1 comments:

Kurt9 said...

Once this task is accomplished, the obvious next step is to scale it up to make multi-cellular "systems".