Análisis termodinámico y metabólico de un sistema biológico células de insecto Spodoptera frugiperda (sf9) y su infección con un virus recombinante Autographa californica nucleopolyhedrovirus (BvGCN4-NA1)

dc.contributorSuárez Méndez, Camilo Alberto
dc.contributorBioprocesos y Flujos Reactivos
dc.creatorFajardo Figueroa, Lina Maria
dc.date.accessioned2023-01-25T21:41:23Z
dc.date.accessioned2023-06-06T23:49:06Z
dc.date.available2023-01-25T21:41:23Z
dc.date.available2023-06-06T23:49:06Z
dc.date.created2023-01-25T21:41:23Z
dc.date.issued2022-10-10
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/83129
dc.identifierUniversidad Nacional de Colombia
dc.identifierRepositorio Institucional Universidad Nacional de Colombia
dc.identifierhttps://repositorio.unal.edu.co/
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/6651545
dc.description.abstractEn el presente trabajo se aborda el análisis de la producción de proteínas recombinantes con interés bio-farmacéutico a través de la tecnología de expresión en células de insecto mediante la infección con baculovirus recombinantes. Esta es una estrategia ampliamente utilizada que aún tiene desafíos en el diseño, modelamiento y entendimiento (Monteiro, 2015). En primer lugar, se analiza bajo una perspectiva termodinámica de caja negra la etapa de crecimiento celular encontrando que su modelamiento es posible a través de una metodología, dirigida principalmente a microorganismos, la cual se puede adaptar a eucariotas con especial consideración en la definición y diferenciación de la fuente de energía, carbono y nitrógeno. En particular, cuando se considera en el análisis una fuente de nitrógeno orgánica, la cual induce un sobreflujo de electrones que pueden terminar en biomasa o en subrpoductos carbonados como lactato. Aunque no fue posible reproducir los escenarios planteados en un modelo metabólico, mediante el análisis metabólico se identificó la importancia de considerar las rutas de asimilación de nitrógeno (orgánico e inorgánico) y el uso de métodos estadísticos como herramienta para la mejora de estos procesos. Finalmente, basado en el análisis de tiempos característicos derivados de cinéticas reportadas para la etapa de infección y producción en la literatura, se encontró que el evento celular que principalmente afecta la homogeneidad y la productividad de las proteínas recombinantes es el evento de unión virus-célula ya que su tiempo característico puede variar considerablemente y afectar otros subprocesos. Además, se encontró que, en la producción de proteínas complejas a nivel intracelular, su expresión se ve favorecida en linajes celulares con velocidades de internalización más bajas. (Texto tomado de la fuente)
dc.description.abstractHere, the analysis of producing recombinant proteins of bio-pharmaceutical interest based on its expression in insect cells through infection with recombinant baculoviruses was addressed. This approach is a widely used strategy that still has challenges in design, modeling and understanding (Monteiro, 2015). First, the cell growth stage was analyzed from a black box thermodynamic perspective, showing that this modeling approach may be used to this biological model, even though it was formerly meant for microorganisms. The methodology can be applied to eukaryotes having special consideration on the definition and differentiation of the energy, carbon, and nitrogen sources. When an organic nitrogen source is considered in the analysis, it induces an overflow of electrons that can end up in biomass or in carbon by-products such as lactate. Although it was not possible to reproduce some scenarios proposed in a metabolic model, the metabolic analysis did show the importance of considering nitrogen assimilation routes (organic and inorganic) and the use of statistical methods as a tool to improve these processes. Finally, based on the analysis of characteristic times derived from kinetics reported for the infection and production stage in literature, it was found that the virus-cell union is the cellular event that mainly affects homogeneity and productivity of recombinant proteins since its characteristic time can vary considerably affecting other subsequent subprocesses. In addition, it is shown that their expression is favored in cell lines with lower internalization rates in the production of complex proteins at the intracellular level.
dc.languagespa
dc.publisherUniversidad Nacional de Colombia
dc.publisherMedellín - Minas - Maestría en Ingeniería - Ingeniería Química
dc.publisherFacultad de Minas
dc.publisherMedellín, Colombia
dc.publisherUniversidad Nacional de Colombia - Sede Medellín
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dc.rightsAtribución-SinDerivadas 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by-nd/4.0/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleAnálisis termodinámico y metabólico de un sistema biológico células de insecto Spodoptera frugiperda (sf9) y su infección con un virus recombinante Autographa californica nucleopolyhedrovirus (BvGCN4-NA1)
dc.typeTrabajo de grado - Maestría


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