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Man-made Protocell Hosts DNA Synthesis
Simon Hadlington, Chemistry World,
June 4, 2008

US researchers have taken a step towards creating a synthetic cell in the laboratory that could resemble the first primitive stirrings of life on Earth. The scientists, from the Howard Hughes Medical Institute in Boston, showed that a mixture of fatty acids and related molecules can spontaneously form stable, hollow vesicles, and that sugars and modified nucleotides can diffuse into this 'protocell'. Once inside, the nucleotides can be induced to polymerise without help from enzymes - a key aspect for prebiotic environments, where complex molecules such as proteins did not exist.

'We are taking a synthetic approach to trying to understand the origins of life, and we are trying to build a protocell model of what we think an early cell might have looked like,' says Jack Szostak, who led the research.

The team systematically investigated a range of fatty acid and related molecules to find a mixture that would self-assemble into permeable vesicles. Phospholipids, which form the basis of 'modern' cell membranes are ruled out because they are highly impermeable and require complex apparatus such as protein pumps and ion channels to allow molecules in and out of the cell.

The researchers showed that a mixture of a fatty acid, its corresponding fatty alcohol, and the glycerol ester of the fatty acid, all combined to spontaneously assemble into vesicles that allowed sugars and modified nucleotides to pass into the vesicle.

To see if the nucleotide could polymerise inside the protocell without the aid of enzymes, the researchers placed a short, simple DNA template 15 bases long within the vesicles. They then added the complementary nucleotide to the medium containing the protocells. 'We saw the monomers diffuse into the cell, bind to the template and spontaneously polymerise,' says Szostak. 'The new chain grew to its full length.'

Szostak says that major questions remain to be answered about how complicated molecules such as nucleotides came into existence and how these then became self-replicating polymers. 'What our model shows is that if something like this did exist on the early Earth, simple cells could take up nutrients from the environment. This represents one of the steps in which we are starting to combine a cell membrane with genetic material to see how they can work together. We are working pretty hard on nucleic acid chemistry and trying to get a more general set of copying reactions.'

Daniel Frankel, who researches protocells at the University of Newcastle in the UK, says that Szostak's latest work is 'very important and very, very exciting. It shows that prebiotically plausible vesicles can take up sugars and nucleotides and this takes the model of the protocell forward significantly.'