Signal and noise propagation in genetic circuits

Interactions between genes in living organisms are intrinsically stochastic. This not only gives rise to phenotypic variation in clonal populations of cells, but also fundamentally limits signaling fidelity and cellular memory. Accurately predicting noise propagation in gene networks is thus crucial for reverse engineering natural networks and designing reliable synthetic genetic circuits. To determine how noise propagates through gene networks we measure, in single bacterial cells, expression variability and correlations between genes in a cascade and correlations with a constitutive gene. We find that noise in a gene is determined by its intrinsic fluctuations, transmitted noise from upstream genes and global noise affecting all genes. Our results imply that the dominant noise sources can be external to any given gene and that even for networks in which no component has significant intrinsic noise, total noise can be significant due to amplification of global fluctuations. We develop a Langevin type model that explains the complex behaviour exhibited by the noises and correlations, and reveals the dominant noise sources from the biochemical characteristics of the individual genes. The model successfully predicts the noises and correlations as the network is systematically perturbed. It also indicates that the additional information from the protein expression distributions can be used to better determine the system parameters and provides the basis for a Monte Carlo simulation method, which allows for fast, approximate simulations of the distributions.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Physics.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Pedraza, Juan Manuel

Advisor dc:contributor.advisor

• Alexander van Oudenaarden.

• Physics.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34402
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34402

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34402