eCHO Systems – Enhancing the CHO cell factory using Systems Biology

On the 13-14th of September,  the 2nd Annual Meeting for the eCHO Systems Innovative Training Network (ITN)  took place in Vienna. The members of the consortium had the opportunity to meet together with the Scientific Advisory board and the Principal Investigators to discuss the progress made so far and share their future plans for the coming year.

The eCHO Systems ITN is a consortium of  four academic partners; Denmark Technical University (DTU), Copenhagen (Denmark), University of Natural Resources and Life Sciences (BOKU), Vienna (Austria), University of Kent (UKent), Canterbury (UK), and Dublin City University (DCU), Dublin (Ireland), together with several industrial partners, including the Austrian Center for Industrial Biotechnology (ACIB) and UCB Pharma.

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The main aims of the network are providing training to 15 PhD students and seeking to significantly advance the Chinese Hamster Ovary (CHO) cell platform for production of biopharmaceuticals. The projects in the consortium are all focused on developing and applying synthetic and systems biology tools to create the next generation CHO cell factory.

Currently, three Early Stage Researchers (ESRs)  are enrolled on the PhD program at Dublin City University: Prashant Kaushik and Ricardo Valdés-Bango Curell, as part of the CHO engineering group at the National Institute for Cellular Biotechnology (NICB), under the supervision of Dr. Paula Meleady and Dr. Niall Barron, and Krishna Motheramgari, as part of the Bioinformatics group at the National Institute for Bioprocessing Research and Training (NIBRT), under the supervision of Dr. Colin Clarke.

During this first year, the students participated in a series of  Network Training Activities (NTAs), which took place at the different partner sites.


dtu_logoCopenhagen: The CHO cell and the 'CHOmics' world 

In September 2015, the first two NTAs took place at DTU in Copenhagen and were organized by Dr. Mikael Rørdam Andersen, Associate Professor at the Department of Biotechnology and Biomedicine, Technical University of Denmark (DTU). These two courses focused on Genome Engineering and Cell Culture Methods and Genome-Scale Science and Modelling, with a special focus on the CHO cell factory and the production of recombinant therapeutic proteins. The students learned about the latest advances in cell engineering and genome-scale science related to the CHO cell platform. The practical part of the course allowed them to get hands-on experience handling CHO cell cultures in bioreactors, monitoring critical culture parameters such as pH and metabolites, and evalute their impact on productivity.

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In addition, the students had the opportunity to visit several manufacturing sites from various biopharmaceutical companies located in the Copenhagen Area, such as Biogen, CMC Biologics and Novo Nordisk A/S. At each site, the students met with industrial experts and discussed the current challenges related to CHO cell factories and recombinant prtein production.

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nicb_nibrt_dcu_logoDublin: How do we make sense of the data?

Later, during the first two weeks of June 2016, the NICB in Dublin hosted the members of the eCHO Systems ITN to attend the second NTA, focused on Advanced Bioinformatics and organized by Dr. Colin Clarke, Principal Investigator in the Bioinformatics group at NIBRT. The topics covered included the acquisition and analysis of large transcriptomic, proteomic and glycomic datasets obtained from CHO cells using a broad range of technologies, from microarrays, Next-Generation Sequencing (NGS), miRNA and proteomics profiling.  During the practical sessions of the course, the students had the chance to work on data from real CHO-based experiments and were able to perform their own bioinformatic analysis. Case studies always aimed to address industry-relevant problems related to production of biopharmaceuticals in CHO cells using a multi-omics bioinformatics approach. In addition, the students had to work in teams on small projects, which required putting into practice all the learned concepts.

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During their stay in Dublin, the eCHO ESRs also had the opportunity to visit the Pfizer manufacturing site in Grange Castle (Dublin, Ireland) and discuss the present and future challenges in recombinant protein production at an industrial scale with on-site experts.

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Alongside with their training, the eCHO crew had the opportunity to get a taste of Irish culture through several social fun activities, such as a day trip to the Wicklow mountains and Glendalough or the visit of the Guinness Storehouse in Dublin.


ukent_logoKent: How do we characterize our valuable products..?

The third NTA took place at the University of Kent, in Canterbury (UK), and was organized by Prof. Dr. Mark Smales, Professor of Industrial Biotechnology, and his collaborators Dr. James Budge and Dr. Tanya Knight. On this occasion, the course was focused on Process Analytical Technologies such as chromatography, mass spectrometry, fluorescence spectroscopy and circular dichroism, applied to recombinant protein production and characterization. During this course, the students also had an extensive amount of laboratory training involving the purification of a monoclonal, its characterization using SDS-PAGE and mass spectrometry, as well as specific applications of the above-mentioned techniques.

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In addition to all the training, social and team building activities were also planned during the stay in Canterbury. Examples of those were a lovely dinner at a traditional English Pub, a guided walking tour around the Canterbury Old Town and a half-day trip to the neighbouring Cliffs of Dover.

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boku_logoVienna: ...and our cells?

Finally, the last NTA was held in Vienna early September 2016. On this occasion the course was organized by Prof. Dr. Nicole Borth, Dr. Jennifer Schoberer and Dr. Markus Schosserer from BOKU. This time, the main topics were Cell Imaging, Flow Cytometry and Presentation Skills. The ESRs had a comprehensive overview of the current techniques for live cell imaging, immunofluorescent staining and flow cytometry applications to characterize and sort cell populations. As usual, a special emphasis was given on the potential of such techniques to analyse CHO cells for specific improved phenotypes such as high producers or fast growing cells.

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The practical sessions on fluorescence microscopy, confocal microscopy, gSTED microscopy and RAMAN microscopy allowed the students to prepare live and fixed biological samples for fluorescent staining and operate by themselves the different types of equipment. The Presentation Skills training was organized by Wolfgang Kainz from Business Theater. Here, the students had the opportunity to be recorded while presenting their Annual Meeting slides. The videos were then analyzed by the group to provide corrections and advice to improve body language and help the students improve their presentations.

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Once more, social activities were not missing in the schedule and the ESRs were given a taste of the rich Viennese lifestyle. Some examples are a guided tour around the city center in Vienna and inside the Schönbrunn, a lovely dinner in the oldest Viennese restaurant and a day trip to the region of Wachau, famous for its vineyards.



euThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 642663


ricRicardo Valdés-Bango Curell
Marie-Curie PhD fellow at NICB, DCU.
eCHO Systems International Training Network (ITN)

Funded by an Early-Stage Researcher Marie Skłodowska-Curie action from the European Comission, as part of the  Innovative Training Network eCHO-systems, my research focuses on the investigation of genetic switches, endogenous or exogenous, for controlled transgene expression in the CHO cell factory and their potential applications in the biopharmaceutical industrial context.

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