Analysis of signal transduction networking using activation ratios

The molecular processes by which information is incorporated and distributed within a cell are termed signal transduction. These pathways allow cells to interact with each other and with their environments and are critical to the proper cellular function in a variety of contexts. Previously developed methods for analyzing signaling networks have been largely ignored, most likely due to their mathematical complexity and difficulty in application. A novel analysis framework was developed to assist in the examination of signaling networks, both to facilitate the reconstruction of previously undetermined pathways as well as to quantitatively characterize interactions between components. This approach, termed activation ratio analysis, involves the ratio between active and inactive forms of signaling intermediates at steady state. The activation ratio of an intermediate is shown to depend linearly upon the concentration of the activating enzyme. The slope of the line is defined as the activation factor, and is determined by the kinetic parameters of activation and inactivation. The mathematical functionality of the activation ratio changes for other signaling network arrangements. It is therefore possible to extract the original network structure from a set of measured activation ratios, with activation factors yielding a measure of activation potential between intermediates. This framework was tested using computational simulations of a small-scale interconnected network, cascades with feedback, and in the presence of experimental noise. In the process, additional tools were developed to automate and evaluate the analysis.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemical Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2004

Author dc:creator

• Femenia, Francisco J

Advisor dc:contributor.advisor

• Gregory Stephanopoulos.

• Chemical Engineering.

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/1721.1/16606

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/16606