Professor Steve Smerdon DPhil BSc (Hons)

Institute of Cancer and Genomic Sciences
Professor of Structural Biology

Contact details

Telephone: +44 (0)121 414 9241
Email: s.j.smerdon@bham.ac.uk
Admin Support: Gemma Jones: g.jones@bham.ac.uk

Address: IBR West
Institute of Cancer and Genomic Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Professor Steve Smerdon is a structural biologist with a long-standing interest in biological signaling processes. For the last twenty years or so, he has been mainly focussed on how cells respond to DNA damage and how protein modifications such as phosphorylation and, more recently, ubiquitylation regulate the timely assembly of protein complexes responsible for maintenance of genomic integrity.

Qualifications

Professor of Structural Biology

PhD in Structural Biology, University of York, 1990
BSc (Hons) in Genetics, University of York, 1987

Biography

Professor Steve Smerdon graduated with a BSc (Hons) in Genetics at the University of York before moving on to his PhD studies with Guy Dodson in the York Structural Biology Laboratory. Following post-doctoral training in Nobel Laureate Tom Steitz’s laboratory at Yale University, he returned to the UK in 1995 to establish an independent programme at the MRC National Institute for Medical Research, eventually becoming Head of the Division of Molecular Structure. He then moved from North London to the Francis Crick Institute as Senior Group Leader prior to his move to Birmingham.

Professor Smerdon was elected member of the European Molecular Biology Organisation in 2009.

Postgraduate supervision

10 PhD students supervised to completion.

Currently one student:

Structure of the fission yeast shelterin complex and its role in telomere maintenance.

Other self-funded projects available.

Research

For the last 20 years or so our primary interest has been in the significance of phosphorylation as a reversible molecular ‘switch’ for multi-protein complex assembly, with a major focus on signalling events that regulate the response to highly genotoxic double-stranded DNA breaks.

Our work has produced the first structures of 14-3-3 proteins (Cell 1997), FHA domains from Chk2 and its yeast orthologue Rad53 (Molecular Cell 2000 & 2002), the Polo-box domain from human Plk1 kinase (Cell 2003), Mob1-family proteins (Science 2013) and BRCT-repeat domains from human Brca1 and Mdc1 (NSMB 2004 & Cell 2005), all in complex with phosphorylated motifs from interacting partners. These structural firsts include a much anticipated study of the FHA-BRCT-repeat region of the Nbs1 signalling component of the DNA break repair ‘MRN’ complex (Cell 2009), More recently, we have used electron microscopy and ion-mobility mass spectrometry to describe the overall architecture of the core hetero-octameric Brca1-A histone deubiquitinase complex, providing some intriguing insights into substrate binding and mechanisms of phospho-dependent Brca1-mediated regulation (Cell Reports 2016).

Current projects build on and extend these previous studies and include:

Nbs1 structure-function relationships in interactions with Mdc1 and other factors
Structure, assembly and regulation of Brca1 complexes.
Chk2 kinase activation and identification of novel substrates and effectors
New chemical/synthetic biology and mass spectrometry approaches for identification of novel DNA damage-dependent interactions and functional DNA-damage phosphosite annotation
Interplay between phosphorylation, ubiquitylation and sumoylation in cell proliferation and apoptosis.

Research Groups and Centres

Other activities

2012 - present: MRC-Technology (Now LifeArc) trustee
2003 - present: Scientific Advisory Board – TwistDX, Cambridge, UK
2017 - 2019: Scientific Advisory Committee - MRC Biomedical NMR Centre
2015 – 2019: Wellcome Trust Molecular Basis of Cell Function Expert Review Group
2012 - 2016: Diamond Light Source Scientific Advisory Committee
2014 - Canadian Light Source Scientific Interim Review Panel
2012 - 2014: Diamond Light Source MX User Group
2008 - 2012: MRC Molecular & Cellular Medicine Board
2006 - 2012: MRC-Technology (Now LifeArc) Governing Body
2012 - MRC Protein Phosphorylation Unit Board Advisory Group
2011 - MRC Oxford Protein Production Facility-UK Review Panel (Chair)
2011 - MRC Mitochondrial Biology Unit Director search committee
2010 - MRC Laboratory of Molecular Biology (Structural Studies Division) QQR Panel
2010 - MRC Laboratory of Molecular Biology (PNAC Division) QQR Panel
2009 - MRC Mitochondrial Biology Unit QQR Panel
2009 - 2011: Diamond Light Source MX Peer Review Panel
2009 - BBSRC Genomics Research Evaluation Panel
2008 - MRC Oncology Pilot Industry Collaboration Panel
2007 - NIH NIAID Structural Genomics of Infectious Pathogens Strategy Group
2005 - 2008: Scientific Advisory Board – Structural Genomics Consortium, Oxford
1998 - NIH NIGMS Structural Genomics PSI 1 Planning Group

Publications

Selected publications since 2009:

Von Morgen, P., Burdova, K., Flower, T.G., Joshi, D., Bineva-Todd, G., Federico, S., O’Reilly, N.J., Boulton, S.J., Smerdon, S.J., Macurek, L., Hořejší, Z. (2017) ‘MRE11 stability is regulated by CK2-dependent interaction with R2TP complex’ Oncogene, 36 4943-4950.

Kyrieleis, O.J.P., McIntosh, P.B., Webb, S., Calder, L.J., Patel, N.A., Martin, S.R., Lloyd, J., Robinson, C.V., Rosenthal, P.B., Smerdon, S.J. (2016) ‘Three-dimensional architecture of the human BRCA1-A histone deubiquitinase core complex’ Cell Reports, 17 3099-3106.

Cherry, A.L., Nott, T.J., Kelly, G., Rulten, S.L., Caldecott, K.W., Smerdon, S.J. (2015) ‘Versatility in phospho-dependent molecular recognition of the XRCC1 and XRCC4 DNA-damage scaffolds by Aprataxin-family FHA Domains’ DNA Repair 35, 116-125.

Larsen, D.H., Hari, F., Clapperton, J.A., Gwerder, M., Gutsche, K., Altmeier, M., Jungmichel, S., Fink, D., Lukas, C., Nielsen, M.L., Smerdon, S.J., Lukas, J., Stucki, M. (2014) ‘The NBS1-TCOF1/Treacle complex controls ribosomal RNA transcription in response to DNA damage’ Nature Cell Biol. 16, 792-803.

Pennell, S., Declais, A-C., Li, J., Haire, L.F., Berg, W., Saldanha, J.W., Taylor, I.A., Rouse, J., Lilley, D.M.J., Smerdon, S.J. (2014) ‘Fan1 activity on asymmetric repair intermediates is mediated by an atypical monomeric VRR-Nuc domain’ Cell Reports, 8, 84-93.

Hořejší, Z., Stach, L., Flower, T.G., Joshi, D., Flynn, H., Skehel, J.M., O’Reilly, N.J., Ogrodowicz, R.W., Smerdon, S.J.*, Boulton, S.J. (2014) ‘CK2-dependent PIH1D1 interactions define substrate specificity of the R2TP co-chaperone complex’ Cell Reports, 7, 19-26.

Rock, J.R., Lim, D., Stach, L., Ogrodowicz, R., Keck, J.M., Jones, M.H., Wong, C.C.L., Yates, J.R., Winey, M., Smerdon, S.J., Yaffe, M.B., Amon, A. (2013) ‘The yeast Hippo pathway is activated by phospho-dependent assembly of signaling complexes’ Science 340, 871-875.

Yata, K., Lloyd, J., Maslen, S., Skehel, M., Smerdon, S.J., Esashi, F. (2012) ‘Plk1 and casein kinase 2 act in concert to regulate Rad51 during recombinational repair’ Mol. Cell 45, 371-383.

Jungmichel, S., Clapperton, J.A., Lloyd, J., Spycher, C., Pavic, L., Li, J., Haire, L.F., Lukas, C., Lukas, J., MacMillan, D., Nielsen, M., Stucki, M., Smerdon, S.J. (2012) 'Molecular basis of ATM and FHA-dependent Mdc1 dimerisation in response to DNA-damage' NAR 40, 3913-3928.

Pennell, S., Westcott, S., Ortiz-Lombardía, M., Patel, D., Li, J., Nott, T., Mohammed, D., Buxton, R.S., Yaffe, M.B., Verma, C. & Smerdon, S.J. (2010) ‘Structural and functional analysis of phosphothreonine-dependent FHA domain interactions. Structure 18, 1587-1595.

Lloyd, J., Chapman, J.R., Clapperton, J.A., Haire, L.F., Hartsuiker, E., Li, J., Carr, A.M., Jackson, S.P., Smerdon, S.J. (2009) 'A supra-modular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA-damage' Cell 139, 100-111.

Nott, T.J., Kelly, G., Stach, L., Li, J., Westcott, S., Patel, D., Hunt, D.M., Howell, S., Buxton, R.S., O'Hare, H.M., Smerdon, S.J. (2009) 'An intra-molecular switch regulates phospho-independent FHA domain interactions in Mycobacterium tuberculosis' Sci. Signal. 2, ra12.

View all publications in research portal