Background

Escherichia coli (E. coli) is a Gram-negative bacterium widely used in pharmaceutical industry as a host for recombinant protein production. The production of recombinant proteins using microbial hosts is usually done in a fed-batch operation mode. The transition to continuous, intensified cultivations promises a reduction of spent media and buffers, smaller equipment downtimes, higher space-time yields leading to an overall more sustainable process. Different continuous cultivation approaches using E. coli strains were already investigated (Kopp et al., 2019; Kittler et al., 2021). Depending on the promoter system, target protein and process complexity, the cultivation strategy needs to be carefully chosen. The implementation of robust and reproducible continuous cultivations in laboratory scale is the basis for intensified and greener (bio)pharmaceutical manufacturing.

[1] J. Kopp, A.-M. Kolkmann, P. G. Veleenturf, O. Spadiut, C. Herwig, and C. Slouka, “Boosting Recombinant Inclusion Body Production—From Classical Fed-Batch Approach to Continuous Cultivation,” Front. Bioeng. Biotechnol., vol. 7, p. 297, Oct. 2019, doi: 10.3389/fbioe.2019.00297.

[2] S. Kittler et al., “Cascaded processing enables continuous upstream processing with E. coli BL21(DE3),” Sci Rep, vol. 11, no. 1, p. 11477, Dec. 2021, doi: 10.1038/s41598-021-90899-9.

Goals

Nowadays, process development is not only driven by economical aspects and steady increase of profit. Ecological aspects, the environmental footprint and reusability aspects are of great importance for future process development. This thesis aims to investigate and quantify the benefit of continuous microbial processing. So called “green metrics” as indicator of the process sustainability will be used to compare classical fed-batch with continuous operation. The thesis will combine laboratory work involving a relevant pharmaceutical protein with a novel cradle-to-gate sustainability analysis of the obtained data.

Methods

• E. coli cultivations in stirred tank bioreactors
• in-line, on-line, at-line bioprocess analytics (off-gas analytics, homogenization, HPLC methods, enzymatic assays, SDS-PAGE)
• energy and water related data collection
• sustainability assessment via green metrics (e.g.,WARIEN)
• data processing using MS Excel or Python packages

Opportunities

We offer a highly interesting, diversified position comprising bioprocess technology and sustainability assessment projected on E. coli processing in a state-of-the-art laboratory.

Working at TU Wien

The work will be done at TU WIEN, Research Area of Biochemical Engineering, and will start on October 1st 2023 (40 h/week). This work is scheduled for 6 months and is compensated with 300 €/month.

Please send application (CV + Cover letter) to Rüdiger Lück. ruediger.lueck@tuwien.ac.at