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From the Lab: Biotechnology

Engineered E. coli bacteria signal environmental changes and dividing cells could mend tissue after heart attacks.

Bacterial Sensors
Engineered E. coli bacteria signal environmental changes

Results: Princeton University and Caltech researchers have genetically engineered E. coli bacteria to give off red or green fluorescent light in response to different concentrations of a cell-signaling molecule secreted by a third type of E. coli. Incubating the three types of E. coli in petri dishes resulted in controllable patterns. In one experiment, the researchers produced concentric circles of different colors, with the signaling cells in the center. Surrounding them were two types of fluorescing cells: one that emitted green light when sensing a high concentration of the signaling molecule, and another that gave off red light at medium concentrations.

Why it Matters: Researchers had previously programmed cells to communicate individually or in small groups. Here the Princeton and Caltech team engineered larger populations of bacteria to work together to form visible patterns that could be used, for example, to signal the presence of a toxic chemical. Because the bacteria produce different signals in response to concentrations of a target chemical, they could flag areas of high concentration as likely sources of wider contamination. In theory, bacteria-based sensors could be more sensitive to a broader range of chemicals than conventional sensors are.

Methods: The researchers, led by Ron Weiss and Frances Arnold, used mathematical models of gene activity to predict the responses of different strains of E. coli to distinct ranges of signaling-molecule concentrations. The researchers then synthesized the strains likely to be most useful by inserting into the E. coli genome desired genes, such as those that code for fluorescent proteins. They then spread a mixture of these strains in petri dishes containing growth media and incubated them overnight. Using a fluorescence microscope, they took pictures of the plates to reveal the different colored patterns.

Next Step: To turn microorganisms into sensors, the researchers must couple their gene networks to receptors that specifically bind to target chemicals. They will also need to design the sensors so that the cells remain alive and stable even outdoors. And they will likely need to devise some kind of control switch to reset or turn off the sensors. – By Corie Lok

Source: Basu, S., et al. 2005. A synthetic multicellular system for programmed pattern formation. Nature 434:1130-4.

Repairing the Heart
Dividing cells could mend tissue after heart attacks

Results: In a study that could have ramifications for heart attack patients, researchers led by Mark Keating at the Harvard Medical School-affiliated Children’s Hospital Boston have coaxed adult mammalian heart muscle cells into dividing by adding two types of chemicals. One blocks an enzyme called p38 MAP kinase, important in the early development of many types of cells; the other comprises protein growth factors. Adding these chemicals to rat heart cells in a lab dish induced 7 percent of them to start dividing. To show that the p38 gene can inhibit heart cell division, the researchers engineered live mice who lacked the gene and found that the duplication and separation of chromosomes in their heart cells – a key step in cell division – increased by more than 90 percent.

Why it Matters: During a heart attack, oxygen-starved cells die, leaving behind damaged tissue. Researchers have long thought that the heart can’t repair itself because its cells can’t divide. This paper suggests that tissue regeneration might be possible. Doctors could potentially administer a drug that triggers heart muscle regrowth in recovering heart attack patients.

Researchers have previously shown that heart cells can divide, but only in strains of lab animals with genetic modifications. Here, the Harvard researchers have shown that they can turn on the cells’ ability to divide using a more therapeutically practical strategy: adding chemicals.

Methods: The researchers studied the effects of p38 inhibition on the major stages of cell division – DNA synthesis, division of the cell’s nucleus, and division of the cell itself–in rat cell cultures and living mice. In one experiment, they stimulated heart muscle cells from 12-week-old rats with growth factors in the presence or absence of a p38 inhibitor. They looked for signs of key molecular events associated with the various stages of cell division.

Next Step: While the researchers demonstrated cell division in a lab dish, they did not demonstrate it in live animals. They are now injecting the inhibitor and growth factors into rats with damaged hearts and looking for signs of regrowth. The researchers will also have to ensure that they can control the cell growth and avoid causing cancer. – By Corie Lok

Source: Engel, F. B., et al. 2005. P38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes and Development 19:1175-87.

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