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Temporal encoding and homeostatic co...

University of California, San Diego.

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Temporal encoding and homeostatic control in the IKK-IkappaB-NF-kappaB signaling system.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Temporal encoding and homeostatic control in the IKK-IkappaB-NF-kappaB signaling system./
Author:	Barken, Derren.
Description:	169 p.
Notes:	Advisers: Alexander Hoffmann; Shankar Subramaniam.
Contained By:	Dissertation Abstracts International68-01B.
Subject:	Biology, Bioinformatics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3250073

Temporal encoding and homeostatic control in the IKK-IkappaB-NF-kappaB signaling system.
Barken, Derren.

Temporal encoding and homeostatic control in the IKK-IkappaB-NF-kappaB signaling system. - 169 p.

Advisers: Alexander Hoffmann; Shankar Subramaniam.

Thesis (Ph.D.)--University of California, San Diego, 2007.

The transcription factor NF-kappaB is part of a signaling system that interprets a variety of physiological stimuli. NF-kappaB regulates numerous genes that play important roles in inter- and intracellular signaling, cellular stress responses, cell growth, survival, and apoptosis. This dissertation is an examination of the hypothesis that dynamic control of NF-kappaB is key to understanding the processing that allows these specific responses. This study investigates the existence, mechanisms, and implications of temporal coding within the IKK-IkappaB-NF-kappaB system.Subjects--Topical Terms:

1018415
Biology, Bioinformatics.

Temporal encoding and homeostatic control in the IKK-IkappaB-NF-kappaB signaling system.
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035 $a (UMI)AAI3250073
035 $a AAI3250073
040 $a UMI $c UMI
100 1 $a Barken, Derren. $3 1029314
245 1 0 $a Temporal encoding and homeostatic control in the IKK-IkappaB-NF-kappaB signaling system.
300 $a 169 p.
500 $a Advisers: Alexander Hoffmann; Shankar Subramaniam.
500 $a Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0025.
502 $a Thesis (Ph.D.)--University of California, San Diego, 2007.
520 $a The transcription factor NF-kappaB is part of a signaling system that interprets a variety of physiological stimuli. NF-kappaB regulates numerous genes that play important roles in inter- and intracellular signaling, cellular stress responses, cell growth, survival, and apoptosis. This dissertation is an examination of the hypothesis that dynamic control of NF-kappaB is key to understanding the processing that allows these specific responses. This study investigates the existence, mechanisms, and implications of temporal coding within the IKK-IkappaB-NF-kappaB system.
520 $a The starting point of this work is a previously published, biochemically detailed ordinary differential equation model of NF-kappaB signaling whose predictions for dynamic xvi responses to a single stimuli (TNF) corresponded with experiments. I extend this model in a number of ways.
520 $a First, I refine its parameters and reaction list. Doing so allows me to improve the model's equilibrium predictions for resting cells. It also leads me to highlight the importance of a second degradation pathway (IKK independent free IkappaB degradation) for steady-state regulation, in addition to IKK induced degradation of complexed IkappaB.
520 $a Second, I apply three additional computational techniques to investigate its signal processing characteristics. Clustering allows me to gain insight into the temporal encoding of IKK, such as the lesser importance of early IKK plateaus and greater impact (and fine-grained regulation) of later IKK plateaus. Information theory guides the design and testing of a mutant cell which loses the ability to distinguish stimuli that are distinguished by wild type cells. Principal component analysis allows me to identify common mechanisms whose alterations have stimulus specific effects, altering the responses to some stimuli much more strongly than others.
520 $a Third, I test and validate its utility against a much wider range of experiments. Using the experimental work of my collaborators, I am able to link simulations to experiments for multiple stimuli, with genetic and pharmacological interventions, and with multiple doses and timings.
520 $a In conclusion, this dissertation breaks new ground in using simulations and experiments to understand temporal control in a cell signaling system of great scientific interest, and develops techniques which have relevance for other efforts to understand cell signaling.
590 $a School code: 0033.
650 4 $a Biology, Bioinformatics. $3 1018415
690 $a 0715
710 2 $a University of California, San Diego. $3 1018093
773 0 $t Dissertation Abstracts International $g 68-01B.
790 $a 0033
790 1 0 $a Hoffmann, Alexander, $e advisor
790 1 0 $a Subramaniam, Shankar, $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3250073