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The Protein Production Small Research Facility (SRF) sits within the Centre for Medicines Discovery (CMD) and provides a high-quality protein production service for both academics and industrial scientists. Our research is based on 16 years of experience in protein production in the Structural Genomics Consortium (SGC), where we used cutting-edge technologies and high-throughput (HTP) platforms to express a plethora of very challenging human proteins for structural and functional analyses. These include integral membrane proteins, intrinsically disordered proteins, and extracellular secreted proteins. We have devised methodologies for HTP cloning in 96-well format to increase the speed of generation of constructs for testing, and miniaturised and streamlined expression platforms for E. coli, insect and mammalian cell cultures for both soluble and membrane proteins. These technologies, tailored by my team enabled the SGC in Oxford to solve more than 2000 human protein structures and fulfil the goals of our awarded grants.

In August 2020, our Protein Production SRF was set up to support internal protein requirements within Oxford, external academic research and industry needs. The range of activities that we offer is provided below. Quality control by intact mass analysis is done on every protein generated via our internal MS SRF (see below).

Protein Production activities offered:

Protein Production Activities

Notable achievements:

  • Generation of high-throughput cloning and expression screening protocols enabling screening of >100,000 96-well plates of constructs in 16 years [1-6].
  • Establishment of protocols and protein engineering to produce an array of epigenetic proteins including bromodomains and lysine demethylases [7-13].
  • Development of expression systems and reproducible protocols to enable screening and production of integral membrane proteins [14-22].
  • Creation of a toolkit of vectors for screening and production of proteins and strategies for identifying protein-protein interactions (Published shortly) [23].
  • Production of a highly reproducible Spike antigen for use in a serology assay platform, developed at the University of Oxford, for identifying antibodies against SARS-CoV-2 [24, 25].

Protein Production activities

Mass Spectrometry SRF

The mass spectrometry facility was set up to provide analytical support for high-throughput protein expression, purification and crystallography. Since 2003, we have developed unrivalled expertise in protein characterisation from thousands of structurally diverse proteins including drug targets and membrane proteins. We support protein production within the Centre for Medicines Discovery (CMD) by maintaining a high standard of quality control across the production pipeline. In addition, we supply the same services across the University, to external academic institutions and industry. We have developed unique methodologies for the analysis of membrane proteins, phosphoproteins, glycoproteins and proteins under native conditions, which are both robust and high-throughput. Mass spectrometry, available in real-time, informs and directs decisions at the bench, as well as providing the quality control essential in a protein production environment.

Mass Spectrometry services offered:

Mass Spectrometry services

Notable achievements:

  • Development of high-throughput methodologies in protein expression [26].
  • Measurement of protein size and conformational changes [27-29].
  • Development of methods for intact membrane protein analysis [19, 30].
  • Absolute quantitation of drugs and metabolites [31-33].
  • Mechanistic description of electrospray.

Contact information:

Protein Production:

Mass Spectrometry:



  1. Gileadi, O., et al., High Throughput Production of Recombinant Human Proteins for Crystallography, in Structural Proteomics: High-Throughput Methods, B. Kobe, M. Guss, and T. Huber, Editors. 2008, Humana Press: Totowa, NJ. p. 221-246.
  2. Savitsky, P., et al., High-throughput production of human proteins for crystallization: The SGC experience. Journal of Structural Biology, 2010. 172(1): p. 3-13.
  3. Strain-Damerell, C., et al., Medium-Throughput Production of Recombinant Human Proteins: Ligation-Independent Cloning, in Structural Genomics: General Applications, Y.W. Chen, Editor. 2014, Humana Press: Totowa, NJ. p. 55-72.
  4. Burgess-Brown, N.A., et al., Medium-Throughput Production of Recombinant Human Proteins: Protein Production in E. coli, in Structural Genomics: General Applications, Y.W. Chen, Editor. 2014, Humana Press: Totowa, NJ. p. 73-94.
  5. Mahajan, P., et al., Medium-Throughput Production of Recombinant Human Proteins: Protein Production in Insect Cells, in Structural Genomics: General Applications, Y.W. Chen, Editor. 2014, Humana Press: Totowa, NJ. p. 95-121.
  6. Strain-Damerell, C. and N.A. Burgess-Brown, High-Throughput Site-Directed Mutagenesis, in High-Throughput Protein Production and Purification: Methods and Protocols, R. Vincentelli, Editor. 2019, Springer New York: New York, NY. p. 281-296.
  7. Keates, T., et al., Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation. New Biotechnology, 2012. 29(5): p. 515-525.
  8. Rose, N., et al., Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases. Journal of medicinal chemistry, 2012. 55(14): p. 6639-6643.
  9. Philpott, M., et al., Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching. Epigenetics and Chromatin, 2014. 7(1): p. 14.
  10. Yu, W., et al., A scintillation proximity assay for histone demethylases. Analytical Biochemistry, 2014. 463: p. 54-60.
  11. Bavetsias, V., et al., 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors. Journal of Medicinal Chemistry, 2016. 59(4): p. 1388-1409.
  12. Johansson, C., et al., Structural analysis of human KDM5B guides histone demethylase inhibitor development. Nature chemical biology, 2016. 12(7): p. 539-545.
  13. Tumber, A., et al., Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells. Cell Chemical Biology, 2017. 24(3): p. 371-380.
  14. Rödstrom, K., et al., A lower X-gate in TASK channels traps inhibitors within the vestibule. Nature. 582: p. 443-450.
  15. Quigley, A., et al., The Structural Basis of ZMPSTE24-Dependent Laminopathies. Science, 2013. 339(6127): p. 1604.
  16. Shintre, C.A., et al., Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proceedings of the National Academy of Sciences, 2013. 110(24): p. 9710.
  17. Dong, Y.Y., et al., K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science, 2015. 347(6227): p. 1256.
  18. Grieben, M., et al., Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2). Nat Struct Mol Biol, 2017. 24(2): p. 114-122.
  19. Dong, Y.Y., et al., Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design. Cell, 2018. 175(4): p. 1045-1058.e16.
  20. Bushell, S., et al., The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K. Nature Communications, 2019. 10: p. Article: 3956 (2019).
  21. Rödström, K.E.J., et al., A unique lower X-gate in TASK channels traps inhibitors within the vestibule. bioRxiv, 2019: p. 706168.
  22. Superti-Furga, G., et al., The RESOLUTE consortium: unlocking SLC transporters for drug discovery. Nature reviews. Drug discovery, 2020. 19(7): p. 429-430.
  23. Bulbrook, D., et al., Tryptophan-Mediated Interactions between Tristetraprolin and the CNOT9 Subunit Are Required for CCR4-NOT Deadenylase Complex Recruitment. Journal of Molecular Biology, 2018. 430(5): p. 722-736.
  24. Emmenegger, M., et al., Early peak and rapid decline of SARS-CoV-2 seroprevalence in a Swiss metropolitan region. medRxiv, 2020: p. 2020.05.31.20118554.
  25. The National SARS-CoV-2 Serology Assay Evaluation Group, T.N.S.-C.-S.A.E.G., Manuscript preprint: Head-to-head benchmark evaluation of the sensitivity and specificity of five immunoassays for SARS-CoV-2 serology on >1500 samples. 2020.
  26. Chalk, R., et al., High-Throughput Mass Spectrometry Applied to Structural Genomics. Chromatography, 2014. 1(4): p. 159-175.
  27. McCorvie, T.J., et al., Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase. Human Molecular Genetics, 2016. 25(11): p. 2234-2244.
  28. Froese, D.S., et al., Structural basis for the regulation of human 5,10-methylenetetrahydrofolate reductase by phosphorylation and S-adenosylmethionine inhibition. Nat Commun, 2018. 9(1): p. 2261.
  29. Froese, D.S., et al., Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking. J Biol Chem, 2015. 290(49): p. 29167-77.
  30. Berridge, G., et al., High-performance liquid chromatography separation and intact mass analysis of detergent-solubilized integral membrane proteins. Analytical Biochemistry, 2011. 410(2): p. 272-280.
  31. Tanner, R., et al., Serum indoleamine 2,3-dioxygenase activity is associated with reduced immunogenicity following vaccination with MVA85A. BMC Infect Dis, 2014. 14: p. 660.
  32. McClenaghan, C., et al., Glibenclamide reverses cardiovascular abnormalities of Cantu syndrome driven by KATP channel overactivity. The Journal of clinical investigation, 2020. 130(3): p. 1116-1121.
  33. Gill, M.R., et al., An 111In-labelled bis-ruthenium(ii) dipyridophenazine theranostic complex: mismatch DNA binding and selective radiotoxicity towards MMR-deficient cancer cells. Chemical Science, 2020. 11(33): p. 8936-8944.