Our research is dedicated to the development and optimization of processes for the manufacturing of biopharmaceutical products with mammalian cell lines. We are focused on the development of new tools to improve critical quality attributes of biopharmaceutical products such as glycosylation or protein aggregation. For this purpose we have established various technologies comprising for example the application of cell culture up to the 20 L scale, miRNA technology as well as glycan and protein aggregation analysis. Another important aspect is the development of new process monitoring tools such as soft sensors based on 2D fluorescence spectroscopy. Currently we have started a new research area dealing with digitalization of bioprocesses. In this context we work on new concepts to apply virtual and augmented reality tools in production processes.

Our research group has hosted master and PhD students as well as post-doctoral researchers since 2011. In a number of projects we collaborate with national and international academic institutions and industrial partners. We are always open to new collaborations and projects in the area of innovative process science and production technologies.

Projects in overview:

Institute members

Researcher

Dr. Jakob Birke, Researcher

Dr. Mohammed Milhim, Researcher

PhD Student

Patrick Schlossbauer

Scientific publications

  • Alina Handl, Ángela I. López-Lorente, René Handrick, Boris Mizaikoff, Friedemann Hesse. Infrared attenuated total reflection and 2D fluorescence spectroscopy for the discrimination of differently aggregated monoclonal antibodies. Analyst 144 (2019), 6334-6341, doi: 10.1039/C9AN00424F.
  • Albert J. Paul, René Handrick, Sybille Ebert, Friedemann Hesse. Identification of process con­ditions influencing protein aggregation in Chinese hamster ovary cell culture. Biotechnol. Bioeng. 115 (2018), 1173-1185, doi: 10.1002/bit.26534.
  • Karen Schwab, Friedemann Hesse. Estimating Extrinsic Dyes for Fluorometric Online Moni­tor­ing of Antibody Aggregation in CHO Fed-Batch Cultivations. Bioengineering 4 (2017), E65, doi: 10.3390/bioengineering4030065.
  • Albert J. Paul, Fabian Bickel, Martina Röhm, Lisa Hospach, Bettina Halder, Nina Rettich, René Handrick, Eva M. Herold, Hans Kiefer, Friedemann Hesse. High-throughput analysis of sub-visible mAb aggregate particles using automated fluorescence microscopy imaging. Anal. Bioanal. Chem. 409 (2017), 4149-4156, doi: 10.1007/s00216-017-0362-2.
  • Karen Schwab, Jennifer Lauber, Friedemann Hesse. Fluorometric In Situ Monitoring of an Escherichia coli Cell Factory with Cytosolic Expression of Human Glycosyltransferase GalNAcT2: Prospects and Limitations. Bioengineering 3 (2016), E32, doi: 10.3390/bioengineering3040032.
  • Karen Schwab, Thomas Amann, Jakob Schmid, René Handrick, Friedemann Hesse. Exploring the capabilities of fluorometric online monitoring on chinese hamster ovary cell cultivations producing a monoclonal antibody. Biotechnol. Prog. 32 (2016), 1592-1600, doi: 10.1002/btpr.2326.
  • Fabian Stiefel, Simon Fischer, Alexander Sczyrba, Kerstin Otte, Friedemann Hesse. miRNA profiling of high, low and non-producing CHO cells during biphasic fed-batch cultivation reveals process relevant targets for host cell engineering. J. Biotechnol. 225 (2016), 31-43, doi: 10.1016/j.jbiotec.2016.03.028.
  • Verena V. Emmerling, Simon Fischer, Fabian Stiefel, Karlheinz Holzmann, René Handrick, Friedemann Hesse, Markus Hörer, Stefan Kochanek, Kerstin Otte. Temperature-sensitive miR-483 is a conserved regulator of recombinant protein and viral vector production in mammalian cells. Biotechnol. Bioeng. 113 (2016), 830-841, doi: 10.1002/bit.25853.
  • Fabian Stiefel, Albert J. Paul, Troisi Jacopo, Angelo Sgueglia, Martina Stützle, Eva M. Herold, Friedemann Hesse. The influence of bisphenol A on mammalian cell cultivation. Appl. Microbiol. Biotechnol. 100 (2016), 113-124, doi: 10.1007/s00253-015-6956-8.
  • Simon Fischer, Albert J. Paul, Andreas Wagner, Sven Matthias, Melanie Geiss, Franziska Schandock, Martin Domnowski, Jörg Zimmermann, René Handrick, Friedemann Hesse, Kerstin Otte. miR-2861 as novel HDAC5 inhibitor in CHO cells enhances productivity while maintaining product quality. Biotechnol. Bioeng. 112 (2015), 2142-2153, doi: 10.1002/bit.25626.
  • Albert J. Paul, Karen Schwab, Nina Prokoph, Elena Haas, René Handrick, Friedemann Hesse. Fluorescence dye-based detection of mAb aggregates in CHO culture supernatants. Anal. Bioanal. Chem. 407 (2015), 4849-4856, doi: 10.1007/s00216-015-8672-8.
  • Andreas B. Diendorfer, Matthias Hackl, Gerald Klanert, Vaibhav Jadhav, Manuel Reithofer, Fabian Stiefel, Friedemann Hesse, Johannes Grillari, Nicole Borth. Annotation of additional evolutionary conserved microRNAs in CHO cells from updated genomic data. Biotechnol. Bioeng. 112 (2015), 1488-1493, doi: 10.1002/bit.25539.
  • Albert J. Paul, Karen Schwab, Friedemann Hesse. Direct analysis of mAb aggregates in mam­malian cell culture supernatant. BMC Biotechnol. 14 (2014), 99, doi: 10.1186/s12896-014-0099-3.
  • Maria de los Milagros Bassani Molinas, Christiane Beer, Friedemann Hesse, Manfred Wirth, Roland Wagner. Optimizing the transient transfection process of HEK-293 suspension cells for protein production by nucleotide ratio monitoring. Cytotechnology 66 (2014), 493-514, doi: 10.1007/s10616-013-9601-3.
  • Karina Brinkrolf, Oliver Rupp, Holger Laux, Florian Kollin, Wolfgang Ernst, Burkhard Linke, Rudolf Kofler, Sandrine Romand, Friedemann Hesse, Wolfgang E. Budach, Sybille Galosy, Dethardt Müller, Thomas Noll, Johannes Wienberg, Thomas Jostock, Mark Leonard, Johannes Grillari,  Andreas Tauch, Alexander Goesmann, Bernhard Helk, John E. Mott, Alfred Pühler, Nicole Borth. Chinese hamster genome sequenced from sorted chromosomes. Nature Biotechnol. 31 (2013), 694-695, doi: 10.1038/nbt.2645.
  • Manuel J.T. Carrondo, Paula M. Alves, Nuno Carinhas, Jarka Glassey, Friedemann Hesse, Otto-Wilhelm Merten, Martina Micheletti, Thomas Noll, Rui Oliveira, Udo Reichl, Arne Staby, Ana P. Teixeira, Henry Weichert, Carl-Fredrik Mandenius. How can measurement, moni­tor­ing, modeling and control advance cell culture in industrial biotechnology? Biotechnol. J. 7 (2012), 1522-1529, doi: 10.1002/biot.201200226

Conference talks

  • Hesse, F. A Rational Strategy for the Reduction of Protein Aggregation in Mammalian Cell Cultures. 5th Biotech Days, Laupheim, 2018
  • Hesse, F. A Rational Strategy for the Reduction of Protein Aggregation in Mammalian Cell Cultures. PEGS Europe, Lisbon, 2017

Patents

  • Friedemann Hesse, Albert J. Paul. Verfahren zur Bestimmung der Zellviabilität. DE102016121808 (A1) – 2017-05-18.
  • Wolfgang Ernst, Jens Pontiller, Friedemann Hesse, Haruthai Thaisuchat. Promoter Sequences. Patent Cooperation Treaty Application (2011), patno: WO11076870.

Entwicklung von M3C-Strategien zur Vermeidung von Produktaggregation in Produktionsprozessen mit Säugerzellen

  • Funding: KPK Pharmazeutische Biotechnologie, MWK Baden-Württemberg

Verbundprojekt: Proteinaggregation bei der Herstellung moderner Biopharmazeutika

  • Funding: BMBF

Identifizierung prozessrelevanter miRNAs in Produktionszelllinien

  • Funding: KPK Pharmazeutische Biotechnologie, MWK Baden-Württemberg