A synthetic circuit for selectively arresting daughter cells to create aging populations.
The ability to engineer genetic programs governing cell fate will permit new safeguards for engineered organisms and will further the biological understanding of differentiation and aging. Here, we have designed, built and implemented a genetic device in the budding yeast Saccharomyces cerevisiae that controls cell-cycle progression selectively in daughter cells. The synthetic device was built in a modular fashion by combining timing elements that are coupled to the cell cycle, i.e. cell-cycle specific promoters and protein degradation domains, and an enzymatic domain which conditionally confers cell arrest. Thus, in the presence of a drug, the device is designed to arrest growth of only newly-divided daughter cells in the population. Indeed, while the engineered cells grow normally in the absence of drug, with the drug the engineered cells display reduced, linear growth on the population level. Fluorescence microscopy of single cells shows that the device induces cell arrest exclusively in daughter cells and radically shifts the age distribution of the resulting population towards older cells. This device, termed the 'daughter arrester', provides a blueprint for more advanced devices that mimic developmental processes by having control over cell growth and death.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Bruno
B
Afonso
Pamela A
PA
Silver
Caroline M
CM
Ajo-Franklin
D002453:Cell Cycle / Q000235:genetics; D005818:Genetic Engineering; D009963:Orotic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics* / Q000254:growth & development
D009963:Orotic Acid; C001242:5-fluoroorotic acid; D009964:Orotidine-5'-Phosphate Decarboxylase