Modeling influenza virus-host cell interactions to support cell line development
Coordinator: Prof. Dr.-Ing. U. Reichl, OvGU Madeburg, Chair of Bioprocess Engineering
Responsible: Jun.-Prof. Dr. T. Frensing, MPI Magdeburg, Bioprocess Engineering Group
Contributors: Tanja Laske (PhD student, OvGU Magdeburg), Mandy Bachmann (PhD student, MPI Magdeburg)
Influenza viruses represent a major burden for global public health and economics. As for all viruses, influenza virus only replicates inside a proper host cell. Thereby, influenza viruses can compensate for their small set of maximal 13 proteins by exploiting host cellular functions.
Genome-wide RNAi screens performed in human cells helped to elucidate cellular proteins and pathways required during influenza A virus replication (Karlas et al., Nature 2010). We aim to genetically manipulate crucial host factors in a human designer cell line in order to establish a high yielding production platform for influenza vaccine manufacturing.
Characterization of modified cell lines during growth and infection will provide the basis for the development of a mathematical model, which covers both changes in cellular pathways and virus production. Therefore, an established model for the intracellular influenza virus replication developed by the Bioprocess Engineering Group (Heldt et al., J Virol 2012) will be extended with relevant cellular factors. The model will improve our understanding of the host-pathogen interactions and support the rational design of high-yield producer cell lines.
This model-driven approach is closely linked to experimental work performed at the Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg (see also).
Academic and industrial partners:
Prof. Dr.-Ing. A. Kienle - Otto-von-Guericke-University of Magdeburg, Institute for Automation Engineering
Prof. Dr. T. Meyer, Dr. A. Karlas - Max Planck Institute for Infection Biology Berlin, Molecular Biology
Dr. D. Wirth, Dr. H. Hauser - Helmholtz Centre for Infection Research Brunswick, Molecular Biotechnology
Dr. M. Lesch Steinbeis gGmbH, Berlin
Dr. V. Sandig ProBioGen AG, Berlin
This joint project “CellSys - Cell Line Development by Systems Biology” (0316189A) is funded by the e:Bio initiative of the Bundesministerium für Bildung und Forschung (BMBF).