Nicola Burgess-Brown

Principal Investigator

University of Oxford

Nicola Burgess-Brown obtained a First Class degree in Applied Biochemical Sciences from the University of Ulster in 1997 and spent the following year working as a molecular biologist for SmithKline Beecham. She received her Ph.D. in Molecular Microbiology “Quorum Sensing and Regulation of Virulence Gene Expression in Porphyromonas gingivalis” at the University of Nottingham in 2001. Nicola returned to industry to work on high-throughput cloning and validation of therapeutic cancer antigens for Oxford Glycosciences and subsequently Celltech R&D Ltd. Since joining the SGC in 2004, Nicola has been responsible for optimising the high-throughput screening processes from cloning to expression and purification of human proteins for structural and functional studies. In June 2009, Nicola developed a similar pipeline for production of human integral membrane proteins (IMPs) using the baculovirus/ insect cell expression system. Since June 2011, Nicola has been the Principal Investigator of Biotechnology, responsible for all biotech research (working with soluble proteins, membrane proteins and epigenetics targets) for the Oxford site.

Research Areas

The Biotechnology group is primarily responsible for generating the pipeline of clones targeted by the SGC in Oxford and determining using high-throughput (HTP) screening methods which proteins are expressed in a soluble and stable form suitable for structural and functional studies. We have developed and optimised protocols for high-throughput cloning, test expression/purification and mass spectrometry analyses, large scale expression and protein production and validation. We screen a wide range of proteins (intracellular, extracellular and integral membrane proteins) using E. coli, baculovirus/insect cell and mammalian (BacMam) expression systems.
The platform established by the Biotechnology team, has enabled the site at Oxford to generate more than 550 novel human protein structures and 5 integral membrane protein structures. The group collaborates and interacts closely with the other SGC teams, to develop methods for increasing protein expression, parallel processing and driving output. In addition to enhancing protein expression levels, we also aim to reduce our cost per structure by seeking alternative cheaper reagents, consumables and increasing throughput further by miniaturising processes and increasing automation where possible. Discovering ways to successfully produce the most challenging human proteins would open many doors to our long-term goals as an organisation of understanding how proteins function independently, in complexes and also how they interact with drug molecules.

Group Members

  • Oktawia Borkowska
  • Hannah Brazier
  • Rod Chalk
  • Matthias Ehebauer
  • Katie Ellis
  • Maciej Kliszczak
  • Katarzyna Kupinska
  • Shubhashish Mukhopadhyay
  • Eneida Parizotto
  • Leela Shrestha
  • Claire Strain-Damerell
  • Aleksandra Szykowska
  • Dong Wang

Publications

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Dong, YY; Pike, AC; Mackenzie, A; McClenaghan, C; Aryal, P; Dong, L; Quigley, A; Grieben, M; Goubin, S; Mukhopadhyay, S; Ruda, GF; Clausen, MV; Cao, L; Brennan, PE; Burgess-Brown, NA; Sansom, MS; Tucker, SJ; Carpenter, EP;
Science. 2015 347:1256-1259. doi:
PMID: 25766236

Medium-throughput production of recombinant human proteins: protein production in insect cells.
Mahajan, P; Strain-Damerell, C; Gileadi, O; Burgess-Brown, NA;
Methods in Molecular Biology. 2014 1091:95-121. doi: 10.1007/978-1-62703-691-7_6
PMID: 24203326

Medium-throughput production of recombinant human proteins: ligation-independent cloning.
Strain-Damerell, C; Mahajan, P; Gileadi, O; Burgess-Brown, NA;
Methods in Molecular Biology. 2014 1091:55-72. doi: 10.1007/978-1-62703-691-7_4
PMID: 24203324

Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.
Rose, NR; Woon, EC; Tumber, A; Walport, LJ; Chowdhury, R; Li, XS; King, ON; Lejeune, C; Ng, SS; Krojer, T; Chan, MC; Rydzik, AM; Hopkinson, RJ; Che, KH; Daniel, M; Strain-Damerell, C; Gileadi, C; Kochan, G; Leung, IK; Dunford, J; Yeoh, KK; Ratcliffe, PJ; Burgess-Brown, N; von Delft, F; Muller, S; Marsden, B; Brennan, PE; McDonough, MA; Oppermann, U; Klose, RJ; Schofield, CJ; Kawamura, A;
Journal of Medicinal Chemistry. 2012 55:6639-6643. doi: 10.1021/jm300677j
PMID: 22724510

A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation.
Lucic, B; Zhang, Y; King, O; Mendoza-Maldonado, R; Berti, M; Niesen, FH; Burgess-Brown, NA; Pike, AC; Cooper, CD; Gileadi, O; Vindigni, A;
Nucleic Acids Research. 2011 39:1703-1717. doi: 10.1093/nar/gkq1031
PMID: 21059676

Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair.
Wang, AT; Sengerová, B; Cattell, E; Inagawa, T; Hartley, JM; Kiakos, K; Burgess-Brown, NA; Swift, LP; Enzlin, JH; Schofield, CJ; Gileadi, O; Hartley, JA; McHugh, PJ;
Genes and Development. 2011 25:1859-1870. doi: 10.1101/gad.15699211
PMID: 21896658

High-throughput production of human proteins for crystallization: the SGC experience.
Savitsky, P; Bray, J; Cooper, CD; Marsden, BD; Mahajan, P; Burgess-Brown, NA; Gileadi, O;
Journal of Structural Biology. 2010 172:3-13. doi: 10.1016/j.jsb.2010.06.008
PMID: 20541610

Large-scale structural analysis of the classical human protein tyrosine phosphatome.
Barr, AJ; Ugochukwu, E; Lee, WH; King, ON; Filippakopoulos, P; Alfano, I; Savitsky, P; Burgess-Brown, NA; Müller, S; Knapp, S;
Cell. 2009 136:352-363. doi: 10.1016/j.cell.2008.11.038
PMID: 19167335

Structure of the human RECQ1 helicase reveals a putative strand-separation pin.
Pike, AC; Shrestha, B; Popuri, V; Burgess-Brown, N; Muzzolini, L; Costantini, S; Vindigni, A; Gileadi, O;
Proceedings of the National Academy of Sciences of USA. 2009 106:1039-1044. doi: 10.1073/pnas.0806908106
PMID: 19151156

High throughput production of recombinant human proteins for crystallography.
Gileadi, O; Burgess-Brown, NA; Colebrook, SM; Berridge, G; Savitsky, P; Smee, CE; Loppnau, P; Johansson, C; Salah, E; Pantic, NH;
Methods in Molecular Biology. 2008 426:221-246. doi: 10.1007/978-1-60327-058-8_14
PMID: 18542867

Codon optimization can improve expression of human genes in Escherichia coli: A multi-gene study.
Burgess-Brown, NA; Sharma, S; Sobott, F; Loenarz, C; Oppermann, U; Gileadi, O;
Protein Expression and Purification. 2008 59:94-102. doi: 10.1016/j.pep.2008.01.008
PMID: 18289875

Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B.
Boyd, RS; Adam, PJ; Patel, S; Loader, JA; Berry, J; Redpath, NT; Poyser, HR; Fletcher, GC; Burgess, NA; Stamps, AC; Hudson, L; Smith, P; Griffiths, M; Willis, TG; Karran, EL; Oscier, DG; Catovsky, D; Terrett, JA; Dyer, MJ;
Leukemia. 2003 17:1605-1612. doi: 10.1038/sj.leu.2402993
PMID: 12886250

2017

Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).
Grieben, M; Pike, AC; Shintre, CA; Venturi, E; El-Ajouz, S; Tessitore, A; Shrestha, L; Mukhopadhyay, S; Mahajan, P; Chalk, R; Burgess-Brown, NA; Sitsapesan, R; Huiskonen, JT; Carpenter, EP;
Nature Structural and Molecular Biology. 2017 24:114-122. doi: 10.1038/nsmb.3343
PMID: 27991905

2016

Structural analysis of human KDM5B guides histone demethylase inhibitor development.
Johansson, C; Velupillai, S; Tumber, A; Szykowska, A; Hookway, ES; Nowak, RP; Strain-Damerell, C; Gileadi, C; Philpott, M; Burgess-Brown, N; Wu, N; Kopec, J; Nuzzi, A; Steuber, H; Egner, U; Badock, V; Munro, S; LaThangue, NB; Westaway, S; Brown, J; Athanasou, N; Prinjha, R; Brennan, PE; Oppermann, U;
Nature Chemical Biology. 2016 12:539-545. doi:
PMID: 27214403

8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors.
Bavetsias, V; Lanigan, RM; Ruda, GF; Atrash, B; McLaughlin, MG; Tumber, A; Mok, NY; Le Bihan, YV; Dempster, S; Boxall, KJ; Jeganathan, F; Hatch, SB; Savitsky, P; Velupillai, S; Krojer, T; England, KS; Sejberg, J; Thai, C; Donovan, A; Pal, A; Scozzafava, G; Bennett, JM; Kawamura, A; Johansson, C; Szykowska, A; Gileadi, C; Burgess-Brown, NA; von Delft, F; Oppermann, U; Walters, Z; Shipley, J; Raynaud, FI; Westaway, SM; Prinjha, RK; Fedorov, O; Burke, R; Schofield, CJ; Westwood, IM; Bountra, C; Müller, S; van Montfort, RL; Brennan, PE; Blagg, J;
Journal of Medicinal Chemistry. 2016 59:1388-1409. doi:
PMID: 26741168

Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis.
Montgomery, AB; Kopec, J; Shrestha, L; Thezenas, ML; Burgess-Brown, NA; Fischer, R; Yue, WW; Venables, PJ;
Annals of the Rheumatic Diseases. 2016 75:1255-1261. doi:
PMID: 26209657

2015

K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.
Dong, YY; Pike, AC; Mackenzie, A; McClenaghan, C; Aryal, P; Dong, L; Quigley, A; Grieben, M; Goubin, S; Mukhopadhyay, S; Ruda, GF; Clausen, MV; Cao, L; Brennan, PE; Burgess-Brown, NA; Sansom, MS; Tucker, SJ; Carpenter, EP;
Science. 2015 347:1256-1259. doi:
PMID: 25766236

2014

Machine-assisted synthesis of modulators of the histone reader BRD9 using flow methods of chemistry and frontal affinity chromatography
Guetzoyan, L; Ingham, RJ; Nikbin, N; Rossignol, J; Wolling, M; Baumert, M; Burgess-Brown, NA; Strain-Damerell, CM; Shrestha, L; Brennan, PE; Fedorov, O; Knapp, S; Ley, SV;
MedChemComm. 2014 5:540-546. doi: 10.1039/c4md00007b
PMID:

Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching.
Philpott, M; Rogers, CM; Yapp, C; Wells, C; Lambert, JP; Strain-Damerell, C; Burgess-Brown, NA; Gingras, AC; Knapp, S; Müller, S;
Epigenetics and Chromatin. 2014 7:14-. doi:
PMID: 25097667

Medium-throughput production of recombinant human proteins: ligation-independent cloning.
Strain-Damerell, C; Mahajan, P; Gileadi, O; Burgess-Brown, NA;
Methods in Molecular Biology. 2014 1091:55-72. doi: 10.1007/978-1-62703-691-7_4
PMID: 24203324

Medium-throughput production of recombinant human proteins: protein production in insect cells.
Mahajan, P; Strain-Damerell, C; Gileadi, O; Burgess-Brown, NA;
Methods in Molecular Biology. 2014 1091:95-121. doi: 10.1007/978-1-62703-691-7_6
PMID: 24203326

2013

Structural insights into functional overlapping and differentiation among myosin V motors
Nascimento, AFZ; Trindade, DM; Tonoli, CCC; De Giuseppe, PO; Assis, LHP; Honorato, RV; Deoliveira, PSL; Mahajan, P; Burgess-Brown, NA; Von Delft, F; Larson, RE; Murakami, MT;
Journal of Biological Chemistry. 2013 288:34131-34145. doi: 10.1074/jbc.M113.521088
PMID:

The structural basis of ZMPSTE24-dependent laminopathies
Quigley, A; Dong, YY; Pike, ACW; Dong, L; Shrestha, L; Berridge, G; Stansfeld, PJ; Sansom, MSP; Edwards, AM; Bountra, C; Von Delft, F; Bullock, AN; Burgess-Brown, NA; Carpenter, EP;
Science. 2013 340:1604-1607. doi: 10.1126/science.1231513
PMID:

2012

Plant growth regulator daminozide is a selective inhibitor of human KDM2/7 histone demethylases.
Rose, NR; Woon, EC; Tumber, A; Walport, LJ; Chowdhury, R; Li, XS; King, ON; Lejeune, C; Ng, SS; Krojer, T; Chan, MC; Rydzik, AM; Hopkinson, RJ; Che, KH; Daniel, M; Strain-Damerell, C; Gileadi, C; Kochan, G; Leung, IK; Dunford, J; Yeoh, KK; Ratcliffe, PJ; Burgess-Brown, N; von Delft, F; Muller, S; Marsden, B; Brennan, PE; McDonough, MA; Oppermann, U; Klose, RJ; Schofield, CJ; Kawamura, A;
Journal of Medicinal Chemistry. 2012 55:6639-6643. doi: 10.1021/jm300677j
PMID: 22724510

The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4.
Watson, AA; Mahajan, P; Mertens, HD; Deery, MJ; Zhang, W; Pham, P; Du, X; Bartke, T; Zhang, W; Edlich, C; Berridge, G; Chen, Y; Burgess-Brown, NA; Kouzarides, T; Wiechens, N; Owen-Hughes, T; Svergun, DI; Gileadi, O; Laue, ED;
Journal of Molecular Biology. 2012 422:3-17. doi: 10.1016/j.jmb.2012.04.031
PMID: 22575888

2011

Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair.
Wang, AT; Sengerová, B; Cattell, E; Inagawa, T; Hartley, JM; Kiakos, K; Burgess-Brown, NA; Swift, LP; Enzlin, JH; Schofield, CJ; Gileadi, O; Hartley, JA; McHugh, PJ;
Genes and Development. 2011 25:1859-1870. doi: 10.1101/gad.15699211
PMID: 21896658

Human SNM1a and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair
Wang, AT; Sengerová, B; Cattell, E; Inagawa, T; Hartley, JM; Kiakos, K; Burgess-Brown, NA; Swift, LP; Enzlin, JH; Schofield, CJ; Gileadi, O; Hartley, JA; McHugh, PJ;
Genes and Development. 2011 25:1859-1870. doi: 10.1101/gad.15699211
PMID:

High-performance liquid chromatography separation and intact mass analysis of detergent-solubilized integral membrane proteins.
Berridge, G; Chalk, R; D'Avanzo, N; Dong, L; Doyle, D; Kim, JI; Xia, X; Burgess-Brown, N; Deriso, A; Carpenter, EP; Gileadi, O;
Analytical Biochemistry. 2011 410:272-280. doi: 10.1016/j.ab.2010.11.008
PMID: 21093405

A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation.
Lucic, B; Zhang, Y; King, O; Mendoza-Maldonado, R; Berti, M; Niesen, FH; Burgess-Brown, NA; Pike, AC; Cooper, CD; Gileadi, O; Vindigni, A;
Nucleic Acids Research. 2011 39:1703-1717. doi: 10.1093/nar/gkq1031
PMID: 21059676

2010

High-throughput production of human proteins for crystallization: the SGC experience.
Savitsky, P; Bray, J; Cooper, CD; Marsden, BD; Mahajan, P; Burgess-Brown, NA; Gileadi, O;
Journal of Structural Biology. 2010 172:3-13. doi: 10.1016/j.jsb.2010.06.008
PMID: 20541610

2009

Structure of the human RECQ1 helicase reveals a putative strand-separation pin.
Pike, AC; Shrestha, B; Popuri, V; Burgess-Brown, N; Muzzolini, L; Costantini, S; Vindigni, A; Gileadi, O;
Proceedings of the National Academy of Sciences of USA. 2009 106:1039-1044. doi: 10.1073/pnas.0806908106
PMID: 19151156

Large-scale structural analysis of the classical human protein tyrosine phosphatome.
Barr, AJ; Ugochukwu, E; Lee, WH; King, ON; Filippakopoulos, P; Alfano, I; Savitsky, P; Burgess-Brown, NA; Müller, S; Knapp, S;
Cell. 2009 136:352-363. doi: 10.1016/j.cell.2008.11.038
PMID: 19167335

2008

Codon optimization can improve expression of human genes in Escherichia coli: A multi-gene study.
Burgess-Brown, NA; Sharma, S; Sobott, F; Loenarz, C; Oppermann, U; Gileadi, O;
Protein Expression and Purification. 2008 59:94-102. doi: 10.1016/j.pep.2008.01.008
PMID: 18289875

High throughput production of recombinant human proteins for crystallography.
Gileadi, O; Burgess-Brown, NA; Colebrook, SM; Berridge, G; Savitsky, P; Smee, CE; Loppnau, P; Johansson, C; Salah, E; Pantic, NH;
Methods in Molecular Biology. 2008 426:221-246. doi: 10.1007/978-1-60327-058-8_14
PMID: 18542867

2005

The structural genomics consortium: High-output structure determination
Gileadi, O; Colebrook, S; Burgess, N; Berridge, G; Haroniti, A; Shrestha, B; Smee, C; Sundstrom, M;
The FASEB Journal. 2005 19:A315-A315. doi:
PMID:

2003

Proteomic analysis of the cell-surface membrane in chronic lymphocytic leukemia: identification of two novel proteins, BCNP1 and MIG2B.
Boyd, RS; Adam, PJ; Patel, S; Loader, JA; Berry, J; Redpath, NT; Poyser, HR; Fletcher, GC; Burgess, NA; Stamps, AC; Hudson, L; Smith, P; Griffiths, M; Willis, TG; Karran, EL; Oscier, DG; Catovsky, D; Terrett, JA; Dyer, MJ;
Leukemia. 2003 17:1605-1612. doi: 10.1038/sj.leu.2402993
PMID: 12886250

2002

LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone.
Winzer, K; Hardie, KR; Burgess, N; Doherty, N; Kirke, D; Holden, MT; Linforth, R; Cornell, KA; Taylor, AJ; Hill, PJ; Williams, P;
Microbiology. 2002 148:909-922. doi: 10.1099/00221287-148-4-909
PMID: 11932438

LuxS-dependent quorum sensing in Porphyromonas gingivalis modulates protease and haemagglutinin activities but is not essential for virulence.
Burgess, NA; Kirke, DF; Williams, P; Winzer, K; Hardie, KR; Meyers, NL; Aduse-Opoku, J; Curtis, MA; Cámara, M;
Microbiology. 2002 148:763-772. doi: 10.1099/00221287-148-3-763
PMID: 11882711

1111

High-performance liquid chromatography separation and intact mass analysis of detergent-solubilized integral membrane proteins
Berridge, G; Chalk, R; Burgess-Brown, NA; Carpenter, EP; Gileadi, O;
Analytical Biochemistry. 1111 :-. doi: 10.1016/j.ab.2010.11.008
PMID:

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