SCAN: Modelling Protein Expression in the Baculovirus/Insect Cells System

Abstract
In the last decade, baculovirus insect cell system (BEVS) has emerged as a powerful and versatile technology for the production of recombinant proteins. Viral structural proteins expressed by BEVS assemble into multimeric structures mimicking virus like particles (VLPs). Therefore, rotavirus VLPs (RLPs), triple layered particles composed of three main protein (VP2, VP6 and VP7), seem to be an obvious candidate for vaccination against rotavirus infection, responsible for higher under-five mortality than AIDS/HIV (~440.000). The main advantages of these particles over already commercial live oral vaccines is that they can mimic the organization and conformation of authentic native particles but lack the viral genome, yielding a safer and potentially cheaper vaccine. Moreover, they can be engineered to contain structural proteins corresponding to different rotavirus serotypes, providing broader protection.

The main drawback relates to the considerable high percentage of waste monomers, incomplete (RLP2/6) and malformed RLP2/6/7, which alone represent well over 80% of total product. Therefore, the focus of this work is the optimization/maximization of RLPs production through the development and implementation of advanced monitoring and control strategies based on a detailed stochastic/structured/segregated model. This mathematical tool combined with precise quantitative methods, will permit to decide optimal control strategies of process state variables involved in the overall process at bioreactor scale, namely the infection kinetics, vDNA replication, mRNA synthesis, protein expression and RLPs assembly.

Short CV
1998-2004 - Degree in Chemical Engineering by Faculdade Ciências e Tecnologia - Universidade Nova Lisboa
2004-2006 - Researcher at Animal Cell Technology Lab in ITQB-UNL/IBET
2006-2008 - PhD fellowship by Fundação para a Ciência e Tecnologia since January of 2006, on "Structured modelling of Rotavirus-like Particle production process: a focus on optimization and control" under supervision of Prof. Manuel J.T. Carrondo and Dr. Rui Oliveira, at Animal Cell Technology Lab in ITQB-UNL/IBET