Grant: Strategic Projects - Group
University of Waterloo
$88,000.00
Development of a model-based optimization strategy for mab production
FY 2009-10
Summary
Mammalian cell culture comprises a major platform for producing a number of high-value biopharmaceuticals,
including enzymes, monoclonal antibodies (Mabs), viral vaccines, hormones and immuno-regulators. This
proposal deals with the development of a novel based optimal bioprocessing methodology for the production of
Mab by the Chinese hamster ovary (CHO) cell line using fed batch culture. The optimization will be based on a
detailed model of the process that will describe both the extracellular metabolite fluxes and the signal
transduction pathways in the cell. The objective will be to find an optimal feeding profile and optimal operating
conditions, including nutrient and temperature profile, to be implemented during the fed-batch process. The
key issue for optimizing the system is the prevention or delay of programmed cell death referred to as
apoptosis. Previous studies have proposed only partial models of the system. Some researchers only modelled
the signal transduction pathways related to apoptosis whereas others only modelled the metabolic extracellular
fluxes during the process.
The current research intends to elucidate the mechanisms leading to apoptosis by accounting for both the
evolution of extracellular metabolite fluxes and their specific interaction with the cellular transduction
pathways responsible for apoptosis. This comprehensive mathematical model, to be used for optimization, will
be validated by experimental monitoring of the levels of metabolites, intracellular and extracellular proteins as
well as the proportions of viable, necrotic and apoptotic cells during the Mab production process.
It is expected that by investigating and addressing the interaction between the extracellular fluxes and the
signal transduction pathways realted to apoptosis, a systematic methodology for obtaining novel optimal
protocols for biopharmaceutical production will result. This will bring about a significant cost saving to the
public regarding currently expensive biopharmaceuticals.
Program
Strategic Projects - Group
Recipient
Location
Ontario, Canada
Recipient Type
Academia
Type
Grant
Source
NSERC's Awards Data
As published
Application id
336055-2006
Name nom
Budman, Hector
Department département
Chemical Engineering
Organization id
33
Institution établissement
University of Waterloo
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2009
Competition year année de concours
2006
Award amount
88000
Program id
STPGP
Program nane en
Strategic Projects - Group
Program name fr
Projets stratégiques - De groupe
Group en
Research partnerships programs
Group fr
Programmes de partenariat
Committee code
1044
Committee name en
Strategic Projects Selection Panel - Food and Bioproducts
Committee name fr
Comité de sélection des projets stratégiques - Aliments et bioproduits
Area of application code
405
Area of application group en
Environment
Area of application group fr
Environnement
Area of application en
Modelling and mathematical simulation of natural processes
Area of application fr
Modélisation et simulation mathématique des processus naturels
Research subject code
1802
Research subject group en
Chemical engineering
Research subject group fr
Génie chimique
Research subject en
Biochemical engineering
Research subject fr
Génie biochimique
Partie
3
Nb partie
3
Application title
Development of a model-based optimization strategy for mab production
Keyword
NA
Application summary
Mammalian cell culture comprises a major platform for producing a number of high-value biopharmaceuticals,
including enzymes, monoclonal antibodies (Mabs), viral vaccines, hormones and immuno-regulators. This
proposal deals with the development of a novel based optimal bioprocessing methodology for the production of
Mab by the Chinese hamster ovary (CHO) cell line using fed batch culture. The optimization will be based on a
detailed model of the process that will describe both the extracellular metabolite fluxes and the signal
transduction pathways in the cell. The objective will be to find an optimal feeding profile and optimal operating
conditions, including nutrient and temperature profile, to be implemented during the fed-batch process. The
key issue for optimizing the system is the prevention or delay of programmed cell death referred to as
apoptosis. Previous studies have proposed only partial models of the system. Some researchers only modelled
the signal transduction pathways related to apoptosis whereas others only modelled the metabolic extracellular
fluxes during the process.
The current research intends to elucidate the mechanisms leading to apoptosis by accounting for both the
evolution of extracellular metabolite fluxes and their specific interaction with the cellular transduction
pathways responsible for apoptosis. This comprehensive mathematical model, to be used for optimization, will
be validated by experimental monitoring of the levels of metabolites, intracellular and extracellular proteins as
well as the proportions of viable, necrotic and apoptotic cells during the Mab production process.
It is expected that by investigating and addressing the interaction between the extracellular fluxes and the
signal transduction pathways realted to apoptosis, a systematic methodology for obtaining novel optimal
protocols for biopharmaceutical production will result. This will bring about a significant cost saving to the
public regarding currently expensive biopharmaceuticals.
