DESIGN AND IMPLEMENTATION OF A BIOLOGICAL CIRCUIT ABLE TO RESPOND TO PRE-EQUILIBRIUM INFORMATION

ANDREAS CONSTANTINOU; ALEJANDRA C VENTURA; ALEJANDRO COLMAN-LERNER

Mar del Plata

Conferencia; 51 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

SAIB

Many cellular processes rely on the ability of cells to sense and respond to chemical information in their immediate surroundings. Cells can achieve this by binding chemical signals (ligand) to specific receptor proteins, that convert the chemical information into intracellular signals to which the cells can respond. Furthermore, different concentrations of ligand may be distinguished by the fraction of bound to unbound receptor. Although this isgenerally only possible for concentrations that do not saturate the receptors, we recently showed that cells? ability todistinguish between ligand concentrations could in theory be expanded into the saturating range, by the utilization ofpre-equilibrium information resulting from the ligand?receptor binding kinetics. We termed this mechanism preequilibriumsensing and signaling (PRESS). Here we explore the possibility of biologically implementing this idea asa simple, controllable genetic circuit. Via computational modeling and experiments we show that repression-basedsensing, aided by slow influx of ligand, generates pre-equilibrium dynamics that may enable cells to distinguishbetween different saturating concentrations of ligand. The work may improve our understanding for how cellsprocess information they receive before signaling reaches steady state, and could be applied to the design of betterbiological sensors.