Biography

Nick Le Brun graduated in 1990 with a first class degree in Chemistry from UEA. Supported through a Wellcome Trust Prize Studentship, he remained at UEA to begin his research career in the area of bioinorganic chemistry under the guidance of Prof Andrew Thomson, FRS OBE and Prof Geoff Moore. He gained his PhD in 1993, and continued his research in the School through a Wellcome Trust Fellowship. In 1996, he moved to the Department of Microbiology, Lund University, Sweden to take up an EMBO Fellowship, in the laboratory of Prof Lars Hederstedt. In 1999 Nick was appointed as Lecturer in biological chemistry at UEA,  and subsequently appointed as Senior Lecturer (2006-2009), Reader (2009-2011), and Professor (2011 - ).


Proteins that contain metal ions (metalloproteins) constitute a diverse and hugely important group. By utilising and fine-tuning the wide range of physical and chemical properties exhibited by metal ions, they fulfil many essential roles in many cellular processes. Nick's research interests lie in understanding how bacterial cells handle essential metal ions, the pathways by which metal-containing proteins are assembled, and the reactivities associated with metalloproteins.

Nick’s research has been funded over the past few years by BBSRC, The Wellcome Trust and EPRSC. He was a member of the BBSRC Pool of Experts (2009-2010) and served as a core member of BBSRC Committee D: Molecules, Cells and Industrial biotechnology from 2010-13. Since 2010, Nick has been Director of the UEA Centre for Molecular and Structural Biochemistry, and from 2014 he is Chair of the UK's Inorganic Biochemistry Discussion Group (IBDG, an Interest Group of the RSC).  In 2015-16 he was a member of RSC Dalton Council and was the Chair of the organising committee for the Dalton 2016 meeting.  Nick was on the editorial board of Journal of Biological Inorganic Chemistry (JBIC) from 2014-17 and is currently an editor for Microbiology.

In 2018 Nick was the recipient of the RSC's Joseph Chatt Award, in recognition of his contributions to the understanding of molecular mechanisms of bacterial gene regulation by environmental levels of oxygen, nitric oxide and iron employing iron-sulfur clusters.

In September 2019, Nick became Head of Chemistry at UEA.

 

Selected Publications

Mechanism of iron- and O2-sensing by the [4Fe-4S] cluster of the global iron regulator RirA.
Pellicer Martinez, M. T., Crack, J. C., Stewart, M. Y. Y., Bradley, J. M., Svistunenko, D. A., Johnston, A. W. B., Cheesman, M. R., Todd, J. D., and Le Brun, N. E.
eLife, 2019, 8, e47804.
DOI: 10.7554/eLife.47804.

NosL is a dedicated copper chaperone for assembly of the Cuz center of nitrous oxide reductase.
Bennett, S. P., Soriano-Laguna, M. J., Bradley, J. M., Svistunenko, D. A., Richardson, D. J., Gates, A. J. and Le Brun, N. E.
Chem. Sci., 2019, 10, 4985 - 4993.
DOI: 10.1039/c9sc01053j.

The crystal structure of the transcription regulator RsrR reveals a [2Fe-2S] cluster coordinated by Cys, Glu and His residues.

Volbeda, A., Pellicer Martinez, M. T., Crack, J. C., Amara, P., Gigarel, O., Munnoch, J. T., Huttchings, M. I., Darnault, C., Le Brun, N. E. and Fontecilla-Camps, J. C.
J. Am. Chem. Soc., 2019, 141, 2367 - 2375.
DOI: 10.1021/jacs.8b10823.

Reaction of O2 with a di-iron protein generates a mixed valent Fe2+/Fe3+ center and peroxide.
Bradley, J. M., Svistunenko, D. A., Pullin, J., Hill, N., Stuart, R. K., Palenik, B., Wilson, M. T., Hemmings, A. M., Moore, G. R. and Le Brun, N. E.
Proc. Natl. Acad. Sci. U.S.A., 2019, 116, 2058 - 2067.
DOI: 10.1073/pnas.1809913116.

M. tuberculosis [4Fe-4S] protein WhiB1 is a four-helix bundle that forms a NO-sensitive complex with SigA and regulates the major virulence factor ESX-1.
Kudhair, B. K., Hounslow, A. M., Rolfe, M. D., Crack, J. C., Hunt, D. M., Buxton, R. S., Smith, L. J., Le Brun, N. E., Williamson, M. P. and Green, J.
Nat. Commun., 2017, 8, 2280.
DOI: 10.1038/s41467-017-02418-y.

Sensing iron availability via the fragile [4Fe-4S] cluster of the bacterial transcriptional repressor RirA.
Pellicer Martinez, M. T., Bermejo Martinez, A., Crack, J. C., Holmes, J. D., Svistunenko, D. A., Johnston, A. W. B., Cheesman, M. R., Todd, J. D., and Le Brun, N. E.
Chemical Science, 2017, 8, 8451 - 8463
DOI: 10.1039/c7sc02801f.

Crystal structures of apo and holo forms of the nitric oxide sensor regulator NsrR reveal the role of the [4Fe-4S] cluster in modulating DNA binding.
A. Volbeda, E. L. Dodd, C. Darnault, J. C. Crack, O. Renoux, M. I. Hutchings, N. E. Le Brun, J. C. Fontecilla-Camps.
Nat. Commum., 2017, 8, 15052.
DOI: 10.1038/ncomms15052.

Mass spectrometric identification of intermediates in the O2 driven [4Fe-4S] to [2Fe-2S] cluster conversion in FNR.
J. C. Crack, A. J. Thomson, N. E. Le Brun
Proc. Natl. Acad. Sci. U.S.A., 2017, 114, E3215-E3223.
DOI: 10.1073/pnas.1620987114.

Kinetic analysis of copper transfer from a chaperone to its target protein mediated by complex formation.

K. L. Kay, L. Zhou, L. Tenori, J. M. Bradley, C. Singleton, M. A. Kihlken, S. Ciofi-Baffoni, N. E. Le Brun
Chem. Comm., 2017, 53, 1397-1400.
DOI: 10.1039/C6CC08966F.

Nitrosylation of nitric oxide-sensing regulatory proteins containing [4Fe-4S] clusters gives rise to multiple iron-nitrosyl complexes.
P. N. Serrano, H. Wang, J. C. Crack, C. Prior, M. I. Hutchings, A. J. Thomson, S. Kamali, Y. Yoda, J. Zhao, M. Y. Hu, E. E. Alp, V. S. Oganesyan, N. E. Le Brun, S. P. Cramer
Angew. Chem. Int. Ed., 2016, 55, 14575-14579.
DOI: 10.1002/anie.201607033.

 

PhD studentships

Two competition funded studentships are available in my lab for an Oct 2020 start. Deadline 25th November. Click on the links below for more information and to submit an application.

 

Studentship 1: Assembly of Nitrous Oxide Reductase, a Key Enzyme in Climate Change (LEBRUN_U20DTP1)

Studentship 2: Iron Storage and Detoxification in Human Ferritins (LEBRUN_U20DTP2)

Note that these studentships are open to home/EU applicants. For those not eligible, I am still happy to hear from prospective students who can bring their own funding! Please get in touch.

 

Career

  • 1987 to 1990 BSc Chemistry at UEA, first class
  • 1990 to 1993 Wellcome Trust PhD Prize Studentship at UEA
  • 1993 to 1995 Wellcome Trust Prize Fellowship at UEA
  • 1996 to 1998 EMBO Long Term Fellowship, Department of Microbiology, Lund University, Sweden
  • 1998 to 1999 Senior Research Associate at UEA
  • 1999 – 2006 Lecturer in Biological Chemistry at UEA.
  • 2006 – 2009 Senior Lecturer in Biological Chemistry at UEA
  • 2009 – 2011 Reader in Biological Chemistry at UEA
  • 2011 to present, Professor of Biological Chemistry at UEA

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