Feedback Regulation and Dosage Compensation in Gene Networks

March 24, 2009
11:00am-12:00pm
Interschool Lab, Room 750 CEPSR
Speaker: Murat Acar, CBCD Fellow, Center for Biological Circuit Design at Caltech

Abstract

Feedback-mediated regulation of gene expression is ubiquitous in gene networks. Positive feedback structures can give rise to bistability or hysteresis while negative feedback loops can help cells tune the frequency of cellular switching between different gene expression states. By using the galactose utilization pathway of the yeast Saccharomyces cerevisiae as a model gene network, we experimentally quantified the contribution of different feedback topologies on gene network activity. We reprogrammed the rates of phenotypic switching between the ON and OFF states of the network with time scales ranging from hours to months. Next, in order to understand how the activity of the network is affected by its size (or dosage), we combinatorially constructed diploid 'network mutant' strains in which either one or two copies of the four regulatory genes (GAL2, GAL3, GAL4, and GAL80) of the network were present. Our results demonstrate that the activity of the galactose regulatory network is robust to variations in network size. Cells could use such a design principle to better cope with variations in network size caused, for example, by genome duplication events.


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