uu.seUppsala universitets publikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Stochastic reaction-diffusion kinetics in the microscopic limit
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi. (ehrenberg)
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
2010 (Engelska)Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, nr 46, s. 19820-19825Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Quantitative analysis of biochemical networks often requires consideration of both spatial and stochastic aspects of chemical processes. Despite significant progress in the field, it is still computationally prohibitive to simulate systems involving many reactants or complex geometries using a microscopic framework that includes the finest length and time scales of diffusion-limited molecular interactions. For this reason, spatially or temporally discretized simulations schemes are commonly used when modeling intracellular reaction networks. The challenge in defining such coarse-grained models is to calculate the correct probabilities of reaction given the microscopic parameters and the uncertainty in the molecular positions introduced by the spatial or temporal discretization. In this paper we have solved this problem for the spatially discretized Reaction-Diffusion Master Equation; this enables a seamless and physically consistent transition from the microscopic to the macroscopic frameworks of reaction-diffusion kinetics. We exemplify the use of the methods by showing that a phosphorylation-dephosphorylation motif, commonly observed in eukaryotic signaling pathways, is predicted to display fluctuations that depend on the geometry of the system.

 

 

Ort, förlag, år, upplaga, sidor
2010. Vol. 107, nr 46, s. 19820-19825
Nyckelord [en]
diffusion-limited, mesoscopic, master equation, Smoluchowski, spatial
Nationell ämneskategori
Biologiska vetenskaper
Identifikatorer
URN: urn:nbn:se:uu:diva-133220DOI: 10.1073/pnas.1006565107ISI: 000284261800042PubMedID: 21041672OAI: oai:DiVA.org:uu-133220DiVA, id: diva2:360450
Tillgänglig från: 2010-11-03 Skapad: 2010-11-03 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
Ingår i avhandling
1. Modelling Approaches to Molecular Systems Biology
Öppna denna publikation i ny flik eller fönster >>Modelling Approaches to Molecular Systems Biology
2010 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Systembiologisk modellering på molekylär nivå
Abstract [en]

Implementation and analysis of mathematical models can serve as a powerful tool in understanding how intracellular processes in bacteria affect the bacterial phenotype. In this thesis I have implemented and analysed models of a number of different parts of the bacterium E. coli in order to understand these types of connections. I have also developed new tools for analysis of stochastic reaction-diffusion models.

Resistance mutations in the E. coli ribosomes make the bacteria less susceptible to treatment with the antibiotic drug erythromycin compared to bacteria carrying wildtype ribosomes. The effect is dependent on efficient drug efflux pumps. In the absence of pumps for erythromycin, there is no difference in growth between wildtype and drug target resistant bacteria. I present a model explaining this unexpected phenotype, and also give the conditions for its occurrence.

Stochastic fluctuations in gene expression in bacteria, such as E. coli, result in stochastic fluctuations in biosynthesis pathways. I have characterised the effect of stochastic fluctuations in the parallel biosynthesis pathways of amino acids. I show how the average protein synthesis rate decreases with an increasing number of fluctuating amino acid production pathways. I further show how the cell can remedy this problem by using sensitive feedback control of transcription, and by optimising its expression levels of amino acid biosynthetic enzymes.

The pole-to-pole oscillations of the Min-proteins in E. coli are required for accurate mid-cell division. The phenotype of the Min-oscillations is altered in three different mutants: filamentous cells, round cells and cells with changed membrane lipid composition. I have shown that the wildtype and mutant phenotypes can be explained using a stochastic reaction-diffusion model.

In E. coli, the transcription elongation rate on the ribosmal RNA operon increases with increasing transcription initiation rate. In addition, the polymerase density varies along the ribosomal RNA operons. I present a DNA sequence dependent model that explains the transcription elongation rate speed-up, and also the density variation along the ribosomal operons. Both phenomena are explained by the RNA polymerase backtracking on the DNA.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2010. s. 57
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 785
Nyckelord
stochastic reaction-diffuion kinetics, antibiotic drugs, efflux pumps, amino acid biosynthesis, Min-system, rRNA operon, transcription
Nationell ämneskategori
Biokemi och molekylärbiologi
Forskningsämne
Biologi med inriktning mot molekylär bioteknik
Identifikatorer
urn:nbn:se:uu:diva-132864 (URN)978-91-554-7941-1 (ISBN)
Disputation
2010-12-16, B21, BMC, Husargatan 3, Uppsala, 13:00 (Engelska)
Opponent
Handledare
Anmärkning
Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 715Tillgänglig från: 2010-11-24 Skapad: 2010-10-27 Senast uppdaterad: 2011-03-21Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Personposter BETA

Elf, Johan

Sök vidare i DiVA

Av författaren/redaktören
Elf, Johan
Av organisationen
MolekylärbiologiMolekylär evolutionBeräknings- och systembiologiScience for Life Laboratory, SciLifeLab
I samma tidskrift
Proceedings of the National Academy of Sciences of the United States of America
Biologiska vetenskaper

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 538 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf