Genetic noise in the cyanobacterial circadian oscillator

Clocks are generally considered as quintessential examples of accurate and precise devices. Biological clocks however, are continually subjected to intracellular and extracellular fluctuations that might reduce the fidelity of this periodic timer. One fundamental limitation that might set an upper bound on the fidelity is the stochastic nature of gene expression creating a noisy intracellular environment. Circadian rhythms, driven by oscillators which provide cells with an internal clock that controls the gene expression program, have been observed in a wide range of organisms from cyanobacteria to mammals. To explore the impact of stochastic expression fluctuations on the performance of the circadian clock, it is necessary to monitor single cells, since population experiments will average out these fluctuations. The cyanobacterium Synechococcus elongatus PCC7942 is an excellent candidate for this study since its core circadian oscillator is well explored. We therefore measured, in single cells, the expression fluctuations of a fluorescent reporter driven by the cyanobacterial circadian oscillator. Repeated microscopic imaging of individual cells and their progeny revealed a robust circadian rhythm, and experiments with cells lacking the proposed central clock proteins confirm the crucial role they play in Synechococcus. Experiments conducted by microscopy and flow cytometry establish that the majority of genetic noise in Synechococcus arises from fluctuations uncorrelated between multiple genes (and therefore does not originate with a global clock noise).

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Physics.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Chabot, Jeffrey R. (Jeffrey Raymond)

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/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/32302

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/32302