Quorum Sensing in Mammalian Cells & A Burden-Proof Genetic Circuit
Plus: More research where biology meets engineering.
The first principles of the universe are atoms and empty space; everything else is merely thought to exist.
Research this week: A gene’s location severely impacts its expression level, a circuit to divide labor in bacteria and genetic circuits to control populations of mammalian cells.
Location, Location, Location
Part of the brilliance of synthesizing genomes — as in the Yeast 2.0 project — is that the new genome can be tweaked, ever so slightly, to enable new functions. For the yeast project, researchers added little bits of ‘code’ that enable chromosomes to be “shuffled,” or mixed up, on demand.
This shuffling was used, in a new study, to understand how the position of a gene within the larger chromosome affects its transcriptional output. Researchers looked at 612 genetic changes and found that genomic position — a gene’s context — can greatly alter both its expression level and its isoforms (mRNAs produced from the same gene, but with different transcription start sites, lengths and so on). The discovery relied on two key technologies: A synthetic yeast chromosome that shuffles genes upon induction of Cre recombinase, and full-length RNA-sequencing via a Nanopore device.
The findings suggest that, when building future genomes with de novo DNA synthesis, each gene’s location should be selected with care.
Read more at Science. Twitter thread by first author, Aaron Brooks, below.
Shoulder the Burden
Synthetic biologists coax cells into doing things that, normally, they would not want to do. Manufacture this drug, sense this molecule, build this material. These are all functions that sap a cell’s internal pool of energy, thus slowing their growth and, often, pushing them to mutate and break the added genes.
For a new study, led by my pal Rory Williams, E. coli bacteria were engineered with a special gene circuit. The circuit is designed so that only cells that differentiate will carry out a burdensome or toxic engineered function. The rest of the cells in the population grow as normal; they don’t carry out the function. It’s a circuit that synthetically divides labor, in other words, to reduce burdensome tasks.
By dividing labor in this way, Williams increased fluorescent protein expression by 4.2-fold in engineered cells, when compared with a population of cells in which each organism was engineered to produce the protein.
This work could help engineered cells persist in the environment over longer time periods, while maintaining their functions.
Read more at bioRxiv.
40(+2) Days and Nights
Another genetic circuit, published this week, enables mammalian cells to communicate via small molecules and tune their population levels in response. It’s a synthetic quorum sensing system. This is, I think, the first mammalian communication system that uses diffusible chemicals, rather than physical contact, to send signals.
The new study used auxin, a plant hormone, as the chemical messenger. Cells were engineered to make, release and sense auxin. Sender-receiver cells were engineered to sense their own population density by producing auxin at a fixed rate, and then sensing the molecule’s concentration in the environment. And in further experiments, researchers made a circuit that coaxes cells into suicide when auxin levels are too high, thus crafting a tool for population control. This circuit was robust to mutations, and carried out its population-controlling function for at least 42 days. The researchers only stopped the experiment because of “technical limitations.”
Read more at Cell.
Thanks for reading,