SmartCell – a general framework for whole-cell modeling and simulation

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(1)UPTEC X 02 021 OCT 2002. ISSN 1401-2138. MARIA ANDÉR. SmartCell – a general framework for whole-cell modeling and simulation. Master’s degree project.

(2) Molecular Biotechnology Programme Uppsala University School of Engineering Date of issue 2002-10. UPTEC X 02 021 Author. Maria Andér Title (English). SmartCell – a general framework for whole-cell modeling and simulation Title (Swedish) Abstract SmartCell is a framework for modeling and simulation of biological processes in whole cells. Modeling is performed in an XML-based model description format, derived from biological concepts, that has been developed as part of the framework. The simulation algorithm is based on mesoscopic kinetics, and supports diffusion and localisation of components in the cell. This work presents a first implementation of the SmartCell framework and an initial assessment of its modeling capacity and predictive power. The general conclusion is that SmartCell is highly accurate for modeling reaction kinetics and diffusion, but suffers from speed limitations for complex models including processes occurring on different time-scales. Keywords whole-cell modeling, computer simulation, mesoscopic, bacterial chemotaxis Supervisors. Luis Serrano European Molecular Biology Laboratories, Heidelberg, Germany Examiner. Måns Ehrenberg Dep of Cell and Molecular Biology, Uppsala university Project name. Sponsors. SmartCell. TTA Technotransfer AB. Language. Security. English Classification. ISSN 1401-2138 Supplementary bibliographical information. Pages. 58 Biology Education Centre. Biomedical Center. Husargatan 3 Uppsala. Box 592 S-75124 Uppsala. Tel +46 (0)18 4710000. Fax +46 (0)18 555217.

(3) SmartCell – a general framework for whole-cell modeling and simulation Maria Andér Sammanfattning Datorsimuleringar har länge använts inom biologin, men det är inte förrän de senaste åren som forskare försökt simulera hela celler. SmartCell är ett program för att beskriva och studera beteendet hos en hel cell. Det finns flera användningsområden som gör simuleringar av biologiska system intressanta. Först och främst för att undersöka om en förklaringsmodell för beteendet hos ett visst system verkar riktig. Datorsimuleringar har också fördelen att egenskaper hos systemet kan mätas exakt och under mycket korta tidsintervall, samt att man undviker de praktiska problem som kan förekomma vid experimentellt arbete. Naturligtvis kommer aldrig datorsimuleringar att ersätta laboratoriearbete, men de kan fungera som ett komplement, och faktiskt ge uppslag till nya experiment. En anledning till att datorsimuleringar på hela celler görs först nu är att modellerna blir mycket komplicerade och utvecklingen därför begränsats av tillgång till snabba datorer. En annan viktig orsak är att forskarna inte haft tillräckligt med kunskap för att modellera cellens funktioner. Båda dessa faktorer är fortfarande aktuella, och verkar begränsande på möjligheterna att göra omfattande cellsimuleringar. I det här arbetet har möjligheterna hos SmartCell som verktyg för datorsimuleringar utvärderats. Den modell som testats är kemotaxis i bakterien Escherichia coli. Med hjälp av kemotaxis kan bakterien analysera sammansättningen av näringsämnen och gifter i sin omgivning och därifrån avgöra vilken rörelseriktning som är mest gynnsam att fortsätta simma i. Många anser att biologin i framtiden alltmer kommer att flyttas in i datorn. Ett nytt tvärvetenskapligt forskningsfält, systembiologin, verkar bekräfta dessa idéer. Systembiologerna förordar en slags "holism" i biologin eftersom man poängterar att ett biologiskt system inte kan förstås annat än i sitt sammanhang och under dynamiska förhållanden. SmartCell och liknande projekt är bara början på detta systemtänkande i biologin som vi med säkerhet kommer att få se mycket mer av i framtiden. Examensarbete 20 p, Civilingenjörsprogrammet i molekylär bioteknik Uppsala universitet, oktober 2002.

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