How are Synthetic Cells made?

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Using a computer analogy, one can think of a cell’s cytoplasm as the hardware and the genome as the operating system. A synthetic cell is created by synthesizing a genome and installing it into a recipient cytoplasm. Original components of the recipient cytoplasm are replaced in early divisions and the synthetic cell takes on a phenotype determined by the synthetic genome.

Recently, researchers at the J. Craig Venter Institute announced that they had made the first synthetic cell by piecing together a genome made from bottled chemicals and transplanting it into a recipient cell. The landmark accomplishment represents a new level of control over the substance of life at the molecular level and one that could lead to ways to make cells that produce vaccines in large quantities and cleaner fuels. scientists explain that the synthetic cell was created as a result of a project to learn how to make a cell with the minimum number of genes possible to live. 

There are various steps involved in the preparation of a synthetic cell. They are:-

  1. The first step in making a synthetic cell is to design the genome. This process happens on the computer. It’s expensive and time-consuming today to synthesize long pieces of DNA in the lab. So the researchers used a computer program to chop the genome from any desired cell(generally bacteria).The computer program adds the sticky sequences at either end of each slice that would enable the pieces to be put back together again.
  2. Then they select the target cells, commonly yeast and E. coli,  that are required to be manipulated. They Stitch the genome fragments  into a circular piece of DNA that makes up the completed synthetic genome. Before the target cell does its work, the DNA fragments must be made Target cell-friendly. In order to do so, we need to add to each set of DNA fragments a short sequence of DNA that pulls the fragments into a loop and makes the fragments friendly to target cells that have been treated to make them amenable to gobbling up DNA.
  3. The target cells are then combined in a solution with ten types of DNA fragments, each of which make up a consecutive sequence of the genome of the original cell chosen. The target cells do the work of putting the fragments back together. This process is repeated until the yeast are putting together larger and larger pieces of the genome. Eventually, some of the target cells will have put together a complete synthetic genome. After testing to verify that a colony has the entire bacterial genome, the researchers grow the cells in a flask to allow them to multiply and produce the genome in large quantities.
  4. The next step is to extract the complete synthetic bacterial genome from the target cell and transplant it into bacterial cells. Extracting the genome from the cell and transporting it is the trickiest part of the process. Genomes are huge molecules. The shear force of water moving around the bare DNA molecules can pull it apart. So the researchers immobilize the DNA in a pellet of gel and take it to another lab, where the transplant recipient cells have been prepared. The recipient cells are a close relative of the cells whose genome is the basis of the synthetic genome. Through trial and error, the researchers have found that there is a particular part of the cells’ cycle of growth and division at which they are most likely to take up the foreign DNA. 

Getting the recipient cells to take up the synthetic genome is in part a matter of chance. A researcher mixes the recipient cells with a chemical solution to make their surfaces fluid and sticky, then adds the cells to the DNA solution. Once mixed, the sticky cells begin fusing with one another. In order to maintain a spherical shape as their surface area is increasing, the cells take on volume from the solution around them. By chance, as they fuse, some of these mega cells take in copies of the genome of the original cell.

Left for about three hours, the cells with more than one genome will divide, creating a mixture of cell types. About one in 100,000 cells has the transplanted genome, which contains an antibiotic-resistance gene. When the cell solution is streaked on plates containing the antibiotic, only those with the transplanted genome survive. Thus, the cell that we have now is a synthetic cell.

The J. Craig Venter Institute successfully created a protocell, a cell that has all the minimum requirements for life, and the only cell on which it is done successfully is Mycoplasma mycoides. Though synthetic cells could prove as a breakthrough in the region of medicine and pharmaceuticals, but using it a heavy financial input and super-computational devices. These top-down approaches have limitations for the understanding of fundamental molecular regulation, since the host organisms have a complex and incompletely defined molecular composition. Also, scientists are yet to achieve the target of creating a new living-cell from chemicals, without using a living cell as its precursor.

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