Resource Limitations Lead to Hidden Interactions in Gene Networks
Synthetic Biology Engineering Evolution Design SEED
Friday, June 12, 2015 - 5:15pm to 6:45pm
Protein production in gene networks relies on the availability of resources necessary for transcription and translation, which are found in cells in limited amount. As various genes in a gene network compete for a common pool of resources, including RNA polymerase and ribosomes, a hidden layer of interactions among genetic circuits arises. In this work, we develop a general modeling framework using deterministic reaction rate equations to account for these interactions. We verified the model with a two-stage activation cascade and a one-stage repression circuit in experiments with E coli. Resource limitations introduce (1) a feed-forward loop in the interaction graph of an activation cascade, which shows counterintuitive negative or biphasic steady-state responses, and (2) a positive auto-regulation in a repression circuit, which leads to bistability confirmed by hysteresis behavior.