Single cell measurements, physiology and cell to cell variation during the activation of the S.cerevisiae pheromone response pathway.

ALEJANDRO COLMAN LERNER; RICHARD YU; ANDREW GORDON; GUSTAVO PESCE; ROGER BRENT

Rostock-Warnemunde, Alemania

Conferencia; Cell Signalling Systems Biology; 2006

QUASI y COSBICS, 6to Programa Marco de la Comisión Europea

We studied the quantitative dynamic behavior of a prototypical eukaryotic signal transduction system, the mating pheromone response pathway in yeast, using fluorescent protein reporters. We studied how faithfully this system relays information. In this talk, I will focus on the sources and control of cell to cell variation in system output. Using different combinations of fluorescent reporters, we found that only a small proportion of total cell-to-cell variation is caused by noise in gene transcription and translation during the response (‘expression noise’). Instead, variation is dominated by differences in the capacity of individual cells to transmit signals through the pathway (‘pathway capacity’) and to express genes into proteins (‘expression capacity’). Our results indicate that various quantitative dynamic phenotypes of this system, including the degree of cell to cell variation, are under genetic control. We have developed higher throughput methods to measure fluorescent reporters in flow cytometry that accurately report changes in system output and cell to cell variation over time and under range of pheromone doses. , and are thus now pursuing whole genome screenings to identify genes that regulate quantitative system behavior. I will present data that begins to dissect the different classes of quantitative mutants. Taken together, the results I will present highlight the importance of a quantitative and dynamic understanding of information carrying systems.