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The bacterial toxin RelE displays codon specific cleavage of mRNAs in the ribosomal A-site
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology.
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2003 In: Cell, Vol. 112, 131-140 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2003. Vol. 112, 131-140 p.
URN: urn:nbn:se:uu:diva-91873OAI: oai:DiVA.org:uu-91873DiVA: diva2:164740
Available from: 2004-05-13 Created: 2004-05-13Bibliographically approved
In thesis
1. Intracellular Flows and Fluctuations
Open this publication in new window or tab >>Intracellular Flows and Fluctuations
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mathematical models are now gaining in importance for descriptions of biological processes. In this thesis, such models have been used to identify and analyze principles that govern bacterial protein synthesis under amino acid limitation. New techniques, that are generally applicable for analysis of intrinsic fluctuations in systems of chemical reactions, are also presented.

It is shown how multi-substrate reactions, such as protein synthesis, may display zero order kinetics below saturation, because an increase in one substrate pool is compensated by a decrease in another, so that the overall flow is unchanged. Under those conditions, metabolite pools display hyper sensitivity and large fluctuations, unless metabolite synthesis is carefully regulated. It is demonstrated that flow coupling in protein synthesis has consequences for transcriptional control of amino acid biosynthetic operons, accuracy of mRNA translation and the stringent response.

Flow coupling also determines the choices of synonymous codons in a number of cases. The reason is that tRNA isoacceptors, cognate to the same amino acid, often read different codons and become deacylated to very different degrees when their amino acid is limiting for protein synthesis. This was demonstrated theoretically and used to successfully predict the choices of control codons in ribosome mediated transcriptional attenuation and codon bias in stress response genes.

New tools for the analysis of internal fluctuations have been forged, most importantly, an efficient Monte Carlo algorithm for simulation of the Markov-process corresponding to the reaction-diffusion master equation. The algorithm makes it feasible to analyze stochastic kinetics in spatially extended systems. It was used to demonstrate that bi-stable chemical systems can display spontaneous domain separation also in three spatial dimensions. This analysis reveals geometrical constraints on biochemical memory circuits built from bistable systems. Further, biochemical applications of the Fokker-Planck equation and the Linear Noise Approximation have been explored.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 63 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 988
Molecular biology, mesoscopic, reaction-diffusion, protein synthesis, amino acid, flow, fluctuations, Molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biotechnology
urn:nbn:se:uu:diva-4291 (URN)91-554-5988-9 (ISBN)
Public defence
2004-06-03, Room B41, Uppsala Biomedical Centre, Husarg. 3, Uppsala, 10:00 (English)
Available from: 2004-05-13 Created: 2004-05-13 Last updated: 2010-01-14Bibliographically approved

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