CVIJOVIC, Maria; SOUEIDAN, Hayssam; KLIPP, Edda; SHERMAN, David James; NIKOLSKI, Macha

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CVIJOVIC, Maria
Max-Planck-Institut für Molekulare Genetik [MPIMG]

SOUEIDAN, Hayssam
Laboratoire Bordelais de Recherche en Informatique [LaBRI]
Models and Algorithms for the Genome [ MAGNOME]

KLIPP, Edda
Max-Planck-Institut für Molekulare Genetik [MPIMG]

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Genome Informatics Series. 2008, vol. 21, p. 114--125

Universal Academy Press Inc.

Résumé en anglais

Thorough knowledge of the model organism S. cerevisiae has fueled efforts in developing theories of cell ageing since the 1950s. Models of these theories aim to provide insight into the general biological processes of ageing, as well as to have predictive power for guiding experimental studies such as cell rejuvenation. Current efforts in in silico modeling are frustrated by the lack of efficient simulation tools that admit precise mathematical models at both cell and population levels simultaneously. We developed a novel hierarchical simulation tool that allows dynamic creation of entities while rigorously preserving the mathematical semantics of the model. We used it to expand a single-cell model of protein damage segregation to a cell population model that explicitly tracks mother-daughter relations. Large-scale exploration of the resulting tree of simulations established that daughters of older mothers show a rejuvenation effect, consistent with experimental results. The combination of a single-cell model and a simulation platform permitting parallel composition and dynamic node creation has proved to be an efficient tool for in silico exploration of cell behavior.< Réduire

Mots clés en anglais

systems biology

ageing and senescence

hybrid hierarchical modeling

yeast

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Exploratory Simulation of Cell Ageing Using Hierarchical Models

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Résumé en anglais

Mots clés en anglais

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