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Application of real time metabolomics to CHO cell optimisation


School of Biological Sciences

Dr K Burgess Wednesday, September 30, 2020 Funded PhD Project (European/UK Students Only)

About the Project

This project is an opportunity to work with the University of Edinburgh and Fujifilm Diosynth Biotechnology UK to explore the optimisation of CHO cell fermentations using metabolomics techniques. Metabolomics has the potential to further elucidate the biochemical pathways functioning in the CHO cell lines, differences in low or high recombinant protein producers, and the change of metabolism during production.

Metabolomics is a relatively new discipline in biology: while, as an ‘omics technology, it aims to provide a broad, unbiased view of a biological system, unlike other omics technologies, metabolomics can profile both medium and cells. Initially, the student will use samples of media and CHO cells supplied by FDBK to, perform conventional untargeted metabolomics. Comparison of the metabolic profile of cells producing similar molecules will be undertaken, e.g. different mAbs, compared to more complex molecule production. Performance parameters will be evaluated in the context of the detected metabolites. A significant part of the project will be to engineer the coupling of a bioreactor system to a mass spectrometer based on technology developed in the Burgess lab. Suitability of the instrument in terms of sampling rate and contamination risks will be assessed and the system may be required to be optimised to ensure reproducible functionality. Once the methodology is established, several cell lines will be analysed and key performance indicators will be evaluated. Finally, the student will explore methodologies to respond to the detected key performance indicators.

Student opportunities: The student will gain in-depth training on the instrumentation in EdinOmics – primarily the Agilent 6560 Ion Mobility QToF and Agilent 6320 ToF mass spectrometers, as well as gaining fundamental insights into liquid chromatography, mass spectrometry and ion mobility spectrometry. The student will also gain the data analysis and statistical skills required to deal with large-scale omics data, along with the specific skills required to deal with the unique complexities of metabolomics. This will include multivariate statistics such as PCA, OPLS-DA, design of experiments and modification of univariate statistics for multiple testing.

The student will be embedded within the prestigious SynthSys centre for synthetic and systems biology, working within the state-of-the-art EdinOmics facility for Biological Mass Spectrometry. The student will also be part of a cohort of students in the FDBK Centre of Excellence in BioProcessing 2.0, and as such will participate in technical meetings at FDBK and also the IBioIC PhD training programme which will enhance the skill set of the student in preparation for their future career. The student will also benefit from a placement at FDBK in the mammalian cell culture laboratories in Process Development under the supervision of an experienced senior scientist. From a combination of observation, training and hands on experimentation, the student will have the opportunity to learn the techniques for preparing and executing mammalian cell culture processes The opportunity of the student to immerse themselves in the FDBK culture will give the student a valuable insight into the mechanisms and challenges of industrial biotechnology.

All interested applicants should send a cover letter and CV to Dr Burgess in the first instance.
http://burgess.bio.ed.ac.uk/
https://fujifilmdiosynth.com/

Equality and Diversity
The School of Biology holds a Silver Athena SWAN award in recognition of our commitment to advance gender equality in higher education: https://www.ed.ac.uk/biology/equality-and-diversity/athena-swan
The University is a member of the Race Equality Charter and is a Stonewall Scotland Diversity Champion, actively promoting LGBT equality. The University has a range of initiatives to support a family friendly working environment. See our University Initiatives website for further information. University Initiatives website: https://www.ed.ac.uk/equality-diversity/help-advice/family-friendly

Funding Notes

This fully-funded 4 year studentship covers tuition fees and stipend. The scholarship is open to UK/EU applicants with at least 3 years residency in the UK immediately prior to the PhD start. Start date January 2021.
The “Visit Website” button on this page will take you to our Online Application checklist. Please complete each step and download the checklist which will guide you through the application process. Application deadline is 5pm Wednesday 30 September 2020.


References

Recent advances in liquid and gas chromatography methodology for extending coverage of the metabolome Haggarty, J. & Burgess, K. EV., 1 Feb 2017, Current opinion in biotechnology. 43, p. 77-85 9 p.

Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
Akpunarlieva, S., Weidt, S., Lamasudin, D., Naula, C., Henderson, D., Barrett, M., Burgess, K. & Burchmore, R., 23 Feb 2017, Journal of proteomics. 155, p. 85-98 14 p.

MetaboCraft: building a Minecraft plugin for metabolomics
Megalios, A., Daly, R. & Burgess, K., 1 Aug 2018, Bioinformatics. 34, 15, p. 2693-2694 2 p.
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