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Problems of high dimension in molecular biology
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för teknisk databehandling. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Numerisk analys. (ndim)
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för teknisk databehandling. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Numerisk analys. (ndim)
2003 (engelsk)Inngår i: Proc. 19th GAMM Seminar Leipzig on High-dimensional problems: Numerical treatment and applications, Leipzig, Germany: Max Planck Institute for Mathematics in the Sciences , 2003, s. 21-30Konferansepaper, Publicerat paper (Fagfellevurdert)
sted, utgiver, år, opplag, sider
Leipzig, Germany: Max Planck Institute for Mathematics in the Sciences , 2003. s. 21-30
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-91875OAI: oai:DiVA.org:uu-91875DiVA, id: diva2:164742
Tilgjengelig fra: 2004-05-13 Laget: 2004-05-13 Sist oppdatert: 2011-11-26bibliografisk kontrollert
Inngår i avhandling
1. Intracellular Flows and Fluctuations
Åpne denne publikasjonen i ny fane eller vindu >>Intracellular Flows and Fluctuations
2004 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2004. s. 63
Serie
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 988
Emneord
Molecular biology, mesoscopic, reaction-diffusion, protein synthesis, amino acid, flow, fluctuations, Molekylärbiologi
HSV kategori
Forskningsprogram
Molekylär bioteknik
Identifikatorer
urn:nbn:se:uu:diva-4291 (URN)91-554-5988-9 (ISBN)
Disputas
2004-06-03, Room B41, Uppsala Biomedical Centre, Husarg. 3, Uppsala, 10:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2004-05-13 Laget: 2004-05-13 Sist oppdatert: 2010-01-14bibliografisk kontrollert
2. Numerical Methods for Stochastic Modeling of Genes and Proteins
Åpne denne publikasjonen i ny fane eller vindu >>Numerical Methods for Stochastic Modeling of Genes and Proteins
2007 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Stochastic models of biochemical reaction networks are used for understanding the properties of molecular regulatory circuits in living cells. The state of the cell is defined by the number of copies of each molecular species in the model. The chemical master equation (CME) governs the time evolution of the the probability density function of the often high-dimensional state space. The CME is approximated by a partial differential equation (PDE), the Fokker-Planck equation and solved numerically. Direct solution of the CME rapidly becomes computationally expensive for increasingly complex biological models, since the state space grows exponentially with the number of dimensions. Adaptive numerical methods can be applied in time and space in the PDE framework, and error estimates of the approximate solutions are derived. A method for splitting the CME operator in order to apply the PDE approximation in a subspace of the state space is also developed. The performance is compared to the most widely spread alternative computational method.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis, 2007. s. 42
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 358
Emneord
master equation, Fokker-Planck equation, stochastic models, biochemical reaction networks
HSV kategori
Forskningsprogram
Beräkningsvetenskap
Identifikatorer
urn:nbn:se:uu:diva-8293 (URN)978-91-554-7009-8 (ISBN)
Disputas
2007-11-30, Room 2446, Polacksbacken, Lägerhyddsvägen 2D, Uppsala, 13:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2007-11-08 Laget: 2007-11-08 Sist oppdatert: 2011-10-26bibliografisk kontrollert

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