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CD Laboratory for next-level biopharmaceuticals in E. coli

Project Leader
Striedner Gerald, Project Leader
Duration:
01.10.2016-30.09.2023
Programme:
Christian Doppler Laboratorien
Type of Research
Basic Research
Project partners
Boehringer Ingelheim Austria GmbH, Dr. Boehringer-Gasse 5-11, 1121 Wien, Austria.
Function of the Project Partner: Partner
Staff
Hahn Rainer, Sub Projectleader
Cserjan Monika, Project Staff
Grabherr Reingard, Project Staff
Egger Esther, Project Staff
Schuller Artur, Project Staff (bis 02.12.2020)
Fink Mathias, Project Staff (bis 30.04.2023)
Weber Andreas, Project Staff
Schiavinato Matteo, Project Staff (bis 31.12.2022)
Mayer Florian, Project Staff (bis 13.01.2023)
Bayer Benjamin, Project Staff (bis 28.02.2022)
Schimek Clemens, Project Staff (bis 30.06.2021)
Klanschnig Marco, Project Staff
Schödl Corinna, Project Staff
Przybylowicz Vanessa, Project Staff (bis 30.11.2022)
Letschnig Lisa, Project Staff
Gutmann Stephan, Project Staff
BOKU Research Units
Institute of Bioprocess Science and Engineering
Funded by
Christian Doppler Forschungsgesellschaft (CDG), Sensengasse 1, 1090 Wien, Austria
Abstract
The vision of this research project is to make Escherichia coli the production system of choice for next-level biopharmaceuticals. To discover, develop, and deliver scientific solutions for efficient production of challenging recombinant proteins with E. coli. The CD laboratory will unite the scientific expertise of university and company research groups focusing on topics along the process chain. Experts in molecular biology, fermentation, downstream processing, and protein analytics jointly elaborate a fundamental and integrated systems knowledge database for development of rational and integrated systems engineering concepts.

The project will focus on two research fields:

Systems characterization and design: Antibody fragments and new scaffolds are selected as representatives for next-level pharmaceuticals. The host cell response to expression of demanding proteins under specified process operation conditions will be analyzed with a broad spectrum of modern analytical techniques. In parallel translation, translocation, localization, periplasmic folding and degradation of recombinant proteins will be investigated in detail by employing specially designed model proteins and/or mutant strains. Improved fundamental understanding of E. coli cell factories will allow for rational host design dedicated to overcome cellular bottlenecks limiting overall process performance.

Integrated up- and downstream processing: Goal is to establish an integrated approach allowing for perfect harmonization of all individual steps of the process chain to gain highest product quality and quantity. The influence of variation in specific process sections on subsequent units and product quality will be investigated and the thus acquired understanding of interrelations will be integrated in optimization strategies. In process engineering concerted design of innovative fermentation and product recovery strategies for periplasmic recombinant proteins will be followed. Special focus will be laid on micro-particle technology representing a new downstream approach.

The company partner Boehringer Ingelheim is a research-driven group of companies dedicated to research, developing, manufacturing and marketing pharmaceuticals that improve health and quality of life. Research & development has been the foundation of Boehringer Ingelheim's success and continues to be the major driver of innovative, new medicines for the treatment of diseases with an unmet therapeutic need. Boehringer Ingelheim BioXcellence™ (Vienna, Austria) is a world-leading biopharmaceutical contract manufacturer. To hold and further develop this position a strong innovation line is needed which can only be achieved by joint academic and industrial research activities.
Keywords
Statistics; Bioinformatics; Microbiology; Molecular biology; Chemical reaction engineering ; Bioprocess technology; Fermentation; Pharmaceutical and drug analysis;
antibody fragments; E.coli; micro particle based cell extraction; process integration; recombinant protein production;
Publications

Schuller, A; Cserjan, M; Jarmer, J; Wagenknecht, M; Reinisch, D; Grabherr, R; Striedner, G (2019): Bioprocess control: Deeper insights into LacI autoregulation and how to exploit it. [Poster]
[257th National Spring Meeting of the American Chemical Society ACS 2019, Orlando, FL, USA, 31.03.2019 - 04.04.2019]

In: American Chemical Society (ACS) (Ed.), ACS National Meeting & Expo 2019 FullText

Schuller, A; Cserjan, M; Jarmer, J; Wagenknecht, M; Reinisch, D; Grabherr, R; Striedner; G (2019): Bioprocess control: Deeper insights into LacI autoregulation and how to exploit it. [Poster]
[RPP10 - 10th International Conference on Recombinant Protein Production, Crete, Greece, 24.04.2019 - 27.04.2019]

In: European Federation of Biotechnology (Ed.), RPP10 - 10th International Conference on Recombinant Protein Production FullText

Cserjan, M; Fink, M; Vazulka, S; Egger, E; Tauer, C; Jarmer, J; Striedner, G; (2018): Production of antibody fragments with plasmid-based and genome integrated T7 E.coli expression systems - evaluation of systems performance in microtiter fed-batch like cultivations.
[European Biotechnology Congress 2018, Moscow, Russian Federation, 11.10.2018 - 12.10.2018]

; ISBN: 2155-952X

Vorträge

Schuller, A; Cserjan, M; Grabherr, R; Striedner, G (2018): Genome integrated expression systems - versatile tools to answer fundamentals in recombinant protein production with E. coli..

12th Symposium of the European Society of Biochemical Engineering Sciences (ESBES2018), SEP 9-12, 2018, Lisbon, PORTUGAL

Schuller, A; Cserjan, M; Jarmer, J; Wagenknecht, M; Reinisch, D; Grabherr, R; Striedner, G (2018): Genome integrated expression systems - versatile tools to answer fundamentals in recombinant protein production with E. coli . [Poster]

10th ÖGMBT Annual Meeting, SEP 17-20, 2018, Vienna, AUSTRIA

Schuller, A; Cserjan, M; Striedner, G (2017): Evaluation of a host RNAP specific promoter for recombinant production of antibody fragments in E. coli .

RPP9 - 9th International Conference on Recombinant Protein Production, APR 23-25, 2017, Dubrovnik, CROATIA

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