Noise and multistability in gene regulatory networks

Proteins are the functional machinery in living cells. Proteins interact with each other and bind to DNA to form so-called gene regulatory networks and in this way regulate the level, location and timing of expression of other proteins. Cells implement feedback loops to create a memory of their gene expression states. In this way, every differentiated cell in a multicellular organism remembers its expression profile throughout its life. On the other hand, biochemical reactions that take place during gene expression involve small numbers of molecules, and are therefore dominated by large concentration fluctuations. This intrinsic noise has the potential to corrupt memory storage and might result in random transitions between different gene expression states. In the first part of my thesis, I will discuss how the fluctuations in gene expression levels are regulated. The results provided the first experimental evidence that cells can regulate noise in their gene expression by tuning their genetic parameters. In the second half of my thesis, I will discuss how cells create memory by experimentally studying a gene regulatory network that implements a positive feedback loop. A positive feedback loop with nonlinear interactions creates two distinct stable gene expression states. A phase diagram, coupled with a mathematical model of the network, was used to quantitatively investigate the biochemical processes in this network. The response of the network depends on its previous history (hysteresis). Despite the fluctuations in the gene expression, the memory of the gene expression state is preserved for a long time for a broad range of system parameters.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Physics.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Ozbudak, Ertugrul M. (Ertugrul Mustafa), 1976-

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/1721.1/16644

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/16644