Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A computational systems biology study of the lambda-lac mutants
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
2007 (English)Manuscript (preprint) (Other academic)
Abstract [en]

We present a comprehensive computational study of some 900 possible “λ-lac” mutants of thelysogeny maintenance switch in phage λ, of which up to date 19 have been studied experimentally(Atsumi & Little, PNAS 103: 4558-4563, (2006)). We clarify that these mutants realise regulatoryschemes quite different from wild-type λ, and can therefore be expected to behave differently, withinthe conventional mechanistic setting in which this problem has often been framed. We verify thatindeed, within this framework, across this wide selection of mutants the λ-lac mutants for the mostpart either have no stable lytic states, or should only be inducible with difficulty. In particular, thecomputational results contradicts the experimental finding that four λ-lac mutants both show stablelysogeny and are inducible. This work hence suggests either that the four out of 900 mutants are special,or that λ lysogeny and inducibility are holistic effects involving other molecular players or othermechanisms, or both. The approach illustrates the power and versatility of computational systemsbiology to systematically and quickly test a wide variety of examples and alternative hypotheses for future closer experimental studies.

Place, publisher, year, edition, pages
2007.
National Category
Condensed Matter Physics
Identifiers
URN: urn:nbn:se:kth:diva-7605OAI: oai:DiVA.org:kth-7605DiVA: diva2:12685
Note

QC 20101119

Available from: 2007-11-12 Created: 2007-11-12 Last updated: 2016-02-02Bibliographically approved
In thesis
1. Gene regulation models of viral genetic switches
Open this publication in new window or tab >>Gene regulation models of viral genetic switches
2007 (English)Licentiate thesis, comprehensive summary (Other scientific)
Abstract [en]

The recent decades of research in molecular biology have resulted in break-throughs concerning our knowledge of the genetic code, protein structures and functions of the different cellular components. With this new information follows an increased interest in constructing computational models of the biological systems. A computational model can range from a description of one specific protein to a complete cell or organism. The aim of a computational model is often to complement the experimental studies and help identify essential mechanisms of a system.

All processes taking place in our cells, from general metabolic processes to cell specific actions, originates from information encoded in our DNA. The first step in transferring the genetic information to a functional protein or RNA, is through the transcription of a gene. The transcription process is controlled by cellular proteins binding to DNA regions called promoters. The term "genetic switch", used in the title of this thesis, refers to a specific change in transcription activity, where one or several promoters get activated or silenced.

In this thesis, I present studies of the regulation mechanisms in two different genetic switches. The first is a switch between two central promoters in the Epstein- Barr virus. This human virus is mostly known for causing the ’kissing disease’, but is also coupled to several cancer types. Infected cells can change between a resting and a proliferating phenotype, depending on which viral promoter is active. In order to understand what causes uncontrolled proliferation in tumors, it is important to understand the regulation of these viral promoters. The other switch is present in the phage λ, a bacterial virus. This virus has one specific promoter region, controlling expression of two proteins that determine if the phage will remain silent (lysogenic) in the host cell, or start producing new viral particles (go lytic). For the Epstein- Barr virus we tested, and confirmed, the hypothesis that the regulation of the two central promoters can be obtained by only one viral and one human protein. Further, we studied the cooperative effects on one of the promoters, showing that steric hindrance at the promoter region results in a more effective switching than with only cooperative binding present. For the bacteriophage λ we studied the genetically altered λ- Lac mutants, presented by Little & Atsumi in 2006. We demonstrate that the experimental results cannot, in terms of its equilibria, be explained by the mechanisms generally believed to be in control of the lysogenic/ lytic switch.

Place, publisher, year, edition, pages
Stockholm: KTH, 2007. x, 60 p.
Series
Trita-CSC-A, ISSN 1653-5723 ; 2007:20
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:kth:diva-4528 (URN)978-91-7178-806-1 (ISBN)
Presentation
2007-11-30, RB35, Hus 16, Albanova, Roslagstullsbacken 35, Stockholm, 13:00 (English)
Opponent
Supervisors
Note
QC 20101119Available from: 2007-11-12 Created: 2007-11-12 Last updated: 2010-11-19Bibliographically approved

Open Access in DiVA

No full text

Other links

http://arxiv.org/PS_cache/arxiv/pdf/0712/0712.3711v1.pdf

Search in DiVA

By author/editor
Werner, MariaAurell, Erik
By organisation
Computational Biology, CB
Condensed Matter Physics

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 60 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf