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Diana Kittig-February 3, 2011 at 12:55 PM UTC

Last year’s artificial cell was created by J. Craig Venter and his colleagues using a “top-down” approach: They replaced the bacterial genome, Mycoplasma genitalium, with a synthetic DNA sequence they designed to contain the minimum genome required for life This is an amazing feat, but all the machinery needed to make cells work is already in the bacterial shell. They just hijacked it with their synthetic genome. 

The artificial cell project was launched this year, and it is planned to adopt a "bottom-up" approach; Libchaber et al. Plan to synthesize a living cell from its basic ingredients. They defined these as cell membranes, which describe the boundaries of cells; devices needed to coordinate metabolic activities; and finally DNA, which is both an information program that drives metabolism and a code that remembers the program, just like Turing tape Same. They believe that the most difficult part is getting these components to work together, as they describe in their progress report.

The membrane part will be easy. Phospholipids are amphiphilic-their lipid tails are hydrophobic, but their negatively charged phosphate groups are hydrophilic-so phospholipid molecules spontaneously form sealed compartments in water. Self-assembled pore molecules are introduced to allow nutrients to enter these compartments and wastes to exit these compartments. However, these porins have not been produced in membranes using only internal gene expression.

The researchers pointed out that "the construction of artificial cells requires the development of an artificial environment." The external medium needs to be much larger than the cells to allow waste to diffuse, and contains a fine-tuned mixture of nucleotides to make RNA, amino acids to make proteins, and ATP to provide Energy, and other ingredients.

The cell also needs to transcribe the DNA sequence into RNA and translate that RNA into protein. For at least the past 25 years, biologists have been using cell-free transcription/translation extracts and have been improving in the process. The first iteration consists of cell extracts that provide translation machinery, supplemented by viral RNA polymerase for transcription. Later, the transcription mechanism from E. coli was recombined from the purified components to form the so-called PURE system. When it is mixed with viral RNA polymerase, you will have a cell-free system in which the entire composition is known. 

However, the lack of other cellular components in these systems is not always a boon. Sometimes proteins made with the PURE system cannot be folded correctly, and additional proteins called chaperones need to be added to solve this problem. 

Recently, this cell-free transcription/translation system has been used for the previously described cell-sized phospholipid vesicles. So, it looks like we are moving towards artificial cells.

There are some caveats at this point. First, it takes a minute for the bacteria to make the protein form a medium-sized gene—from the beginning of gene transcription to a fully functional protein. Cell-free systems cannot start to approach this rate, in part because they must operate at an order of magnitude lower than the protein concentration in the cell. In addition, we may not be able to put all the genes needed for life under the control of a single viral polymerase-these polymerases are too limited to process a large enough genome. Finally, these systems have no built-in systems for removing old and possibly damaged RNA and proteins. 

Then there is the genetic problem. The work of Mycoplasma genitalium shows that it takes about 200-400 genes to make a self-replicating cell. This is too big for a typical DNA vector we can manipulate. It is also too big for a simple, always-on regulatory switch. The genome of the bacteriophage Lambda has 30 proteins, which may be the most well-studied genetic network in history, but it is still not fully understood. 

In order to program the cell to self-replicate—remember, this is the goal here—the author believes that combining small DNA subprograms may be best. Many of these programs are already available, especially those in BioBricks Foundation. These procedures were originally copied from living organisms, but they can be recombined in unique ways, and some new procedures have been produced. But the artificial life team admits that developing DNA programs that are sufficient to drive cells is a major obstacle.

Another major issue is to coordinate the activities of the information contained in DNA with non-genetic material. For example, during cell division, a new membrane must be synthesized, and it must divide as DNA replicates in order to evenly distribute genetic information between two daughter cells.

So, before we make this matter work, we have many obstacles. But we don't necessarily have to make it run so well in the beginning. An interesting aspect of the "bottom-up" approach is that it allows us to better understand cell evolution. The author writes, “Assembling synthetic cells reveals the importance of the physical aspects regulated in the body by an evolved gene network.” Therefore, building a unit from scratch can tell us what we really need and the problems we encounter along the way. , For better or for bad.

PNAS, 2011. DOI: 10.1073/pnas.1017075108 (about DOI).

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