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Doctoral Thesis
DOI
10.11606/T.87.2018.tde-22102018-180313
Document
Author
Full name
Manuel Filgueira Barral
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Augusto, Elisabeth de Fatima Pires (President)
Ferreira, Newton Libânio
Fleury, Agenor de Toledo
Gomez, José Gregorio Cabrera
Tonso, Aldo
Title in Portuguese
Modelo cinético não-estruturado para crescimento e produção de glicoproteína recombinante do vírus da raiva em linhagem S2 de células de Drosophila melanogaster.
Keywords in Portuguese
Drosophila melanogaster S2
Células de inseto
Glicoproteína do vírus rábico
Metabolismo
Modelagem matemática
Modelo não-estruturado
Proteína recombinante
Abstract in Portuguese
Linhagem de células de inseto S2 foram cultivadas em meio TC100 suplementado em reator bubble free de 1.5 L e para estudar o seu crescimento e expressão da glicoproteína G do vírus da raiva (RVGP). Os dados permitiram propor um modelo matemático que reproduz o crescimento e produção da glicoproteína e que considera oito variáveis de estado e vinte parâmetros cinéticos. O modelo considera a velocidade específica de crescimento limitada por glicose, glutamina e glutamato e inibida por NH4+; consumo e formação de glutamina; velocidade específica de morte limitada por NH4+ e inibida por glicose; velocidade específica de produção de NH4+ e de GPV associada ao crescimento e a degradação de GPV. As concentrações de oxigênio dissolvido (pO2), glicose e glutamina foram modificadas para se avaliar a sua influência na velocidade específica de crescimento máxima e nos fatores de conversão. Os parâmetros do modelo foram ajustados usando a técnica de otimização dos poliedros flexíveis e as equações diferenciais do modelo foram integradas pelo método de Gear.
Title in English
Unstructured kinetic modelling for growth and recombinant rabies virus glycoprotein production in a S2 strain cell line of Drosophila melanogaster.
Keywords in English
Drosophila melanogaster S2
Insect cells
Mathematical modeling
Metabolism
Rabies virus glycoprotein
Recombinant protein
Unstrutured model
Abstract in English
S2 cell strain from Drosophila melanogaster were cultivated in supplemented TC100 media in reactor "bubble free" to study their growth and expression of glycoprotein G of rabies virus (RVGP). The data allowed proposing a mathematical model that reproduces the growth and production of glycoprotein and that consider eight state variables and twenty kinetic parameters. The model considers the specific growth rate limited by glucose glutamine and glutamate and inhibited by NH4+ consumption and formation of glutamine, specific death rate limited by NH4+ and inhibited by glucose; production specific rate of NH4+ and RGPV associated with growth and degradation of RGPV. The concentrations of dissolved oxygen (pO2), glucose and glutamine were varied to evaluate their influence on maximum specific growth rate and conversion factors. The model parameters were adjusted using the flexible polyhedron optimization method and the differential equations of the model were integrated by the method of Gear.
 
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Publishing Date
2018-10-22
 
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