Prof Michael Overduin PhD

 

Professor Of Structural Biology

School of Cancer Sciences

Contact details

Telephone 0121 414 3802

Fax 0121 414 4486

Email m.overduin@bham.ac.uk

School of Cancer Sciences
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

About

Michael Overduin is the Professor of Structural Biology within the School of Cancer Sciences of the University of Birmingham, and Executive Director of The Henry Wellcome Building for Biomolecular NMR Spectroscopy.

Qualifications

  • PhD in Biochemistry, The Rockefeller University, USA 1993
  • BSc in Biology, Wilfrid Laurier University, Canada 1988

Biography

Michael Overduin is the Professor of Structural Biology within the School of Cancer Sciences of the University of Birmingham, and Executive Director of The Henry Wellcome Building for Biomolecular NMR Spectroscopy.

Michael graduated with a BSc in Biology from Wilfrid Laurier University, Canada in 1988. He received his PhD in Biochemistry, Genetics and Physical Chemistry from The Rockefeller University in 1993. Michael then post-doctored at the University of Toronto for two years, prior to joining the University of Colorado Health Sciences Center as an Assistant Professor of Pharmacology in 1995. While there, Michael helped to establish a new NMR spectroscopy facility with funding from the Howard Hughes Medical Institute and the Program in Biomolecular Structure. He was promoted to Associate Professor by the University of Colorado School of Medicine in 2002.

In 2003, Michael moved to Birmingham as the Professor of Structural Biology, and was awarded JREI and Joint Infrastructure funding from HEFCE and the Wellcome Trust to establish the UK’s national 900 MHz NMR facility. He serves as Executive Director of the Henry Wellcome Building for Biomolecular NMR Spectroscopy (HWB•NMR), which is now an internationally recognised, large scale scientific facility with a global community of users and collaborators.

Since moving to the UK in 2003, Michael has been awarded over £12m in research funding from the BBSRC, Cancer Research UK, European Commission, MRC, and Wellcome Trust. In 2009, he became the Head of the Structural Biology & Biomarkers Theme in order to develop the University’s translational activities, including building drug discovery partnerships, and stimulate collaborative research into biodiagnostics. Michael led international EU PRISM and Japan Partnering consortia to broaden the take-up of membrane protein analysis and production technologies, and initiated the WW-NMR consortium of international large scale NMR facilities, which has been awarded funding from the EU’s IRSES program.

Commercial outputs include the patented styrene maleic acid lipid particle (SMALP) system, which has been used by a range of academic and industry groups for the analysis and exploitation of transmembrane protein targets. He formed Science Capital in 2010 to help bring together scientists, investors and business experts, and organises meetings to enable partnerships to be formed.

Among Michael’s awards are a Royal Society Wolfson Research Merit Award (2004-2009), University of Birmingham Chair of Structural Biology (2003), University of Colorado Department of Pharmacology Faculty Excellence in Research Award (2001), National Institutes of Health FIRST Award (1998), Pew Scholar Award (1998), Basil O'Conner Award (1998), Howard Hughes Medical Institute Junior Faculty Award (1997), Wilfrid Laurier University Alumnus of the Year (1995), National Cancer Institute of Canada Postdoctoral Fellowship (1993), and Wilfrid Laurier University Gold Medal in Biology (1988).

Teaching

Cancer Signaling to Cures, MBChB, University of Birmingham Medical School

Postgraduate supervision

  • Akhtar, Nazia: (2009 – present, MRC DTA Training Programme), Supervisors: Michael Overduin, Jane McKeating and Mark Jeeves
  • Al-Jassar, Caezar (2008 – present, MRC DTA Training Programme), Supervisors: Michael OVerduin, Martyn Chidgey
  • Brunecky, Roman: University of Colorado Health Sciences Center PhD student (Pharmacology Program) with Michael Overduin from 2001-2003, now a Scientist III at NREL.
  • Cheever, Matthew L: University of Colorado Health Sciences Center PhD student (Molecular Biology Program) from 1999-2004 with Michael Overduin, now a Senior Scientist at Bayer CropScience.
  • Davis, Vicky (2009 Wellcome Trust Combined Training Programme), Supervisors: Michael Overduin, Mark Jeeves
  • Enmon, Jennifer T: University of Colorado - Boulder PhD student with Michael Overduin from 1997-2000, now an European Patent Attorney Trainee at  Vossius & Partner
  • Gopalasingam, Piraveen (2009 – present, CR-UK PhD Training Programme), supervisors: Michael Overduin and Mark Jeeves
  • Maderbocus, Riyaz (2008 – present, MRC DTA Training Programme), Supervisors: Michael Overduin, Tim Knowles, Ian Henderson
  • Tokonzaba, Etienne: University of Colorado Health Sciences Center PhD student (Pharmacology Program) with Michael Overduin from 2001-2003, now a postdoc at the Dermatology and Stem Cell Department, University of Colorado Denver 
  • Tong, Mike: University of Birmingham with Michael Overduin, supported by BBSRC Industrial CASE Studentship and GlaxoSmithKline from 2006-2009, now a postoc with Marcus Seeliger at the Stony Brook University Medical School

Research

Our research focuses on cancer and infectious disease mechanisms. Primary targets include phosphatases and kinases and their regulatory domains, as well as membrane associated systems including phosphoinositide binding domains, G-protein coupled receptors and tetraspanins. We seek to understand how their three dimensional structures, flexibilities and molecular interactions explain their biological localisations and signalling activities.

Specific projects include:

We are elucidating how proteins including FAPP2 bind to and reshape the Golgi membrane into thin tubules that are pinched off to traffic to the cell surface. A wedge mechanism explaining how tubules are formed by the insertion of pleckstrin homology domains into the bilayer is being developed.

The changes in the conformation and activity of a Ser/Thr kinase which is amplified during breast cancer progression are being analysed by nuclear magnetic resonance spectroscopy (NMR), small angle X-ray scattering (SAXS) and X-ray crystallography. The effects of calmodulin and inhibitor binding include conformational changes that propagate across the enzyme structure and suggest novel sites for intervention.

The mechanisms of membrane recruitment by oncogenic protein phosphatases are being characterised by NMR. We have obtained resolved NMR spectra of several targets by solution condition screening, enabling characterisation of their solution structures and interactions. The lipid binding surfaces and specificities are diverse, and localise the proteins to distinct subcellular and membrane destinations.

The structures of the components of the beta barrel assembly machine (BAM) proteins used by pathogenic bacteria are being revealed by NMR and small angle X-ray scattering. Understanding how proteins are folded up inside the membrane that surrounds bacteria may provide new targets for the discovery of next generation antibiotics to combat a wide range of infectious diseases.

We have developed a new bionanoparticle system to purify and solubilise transmembrane proteins without detergents, thus circumventing one of the major bottlenecks of drug discovery for transmembrane receptors. A styrene maleic acid co-polymer transfers membrane proteins directly into 11 nanometer diameter discs that are soluble, stable and easy to work with, and stabilise membrane proteins with their activities and structures intact.

Other activities

  • Executive Director, The Henry Wellcome Building for Biomolecular NMR Spectroscopy (2004 – present)
  • Executive Committee Member, Honorary Secretary and Chair of Science and Medicine Subcommittee, The Lunar Society (2006-present)
  • Associate Editor, Journal of Chemical Biology and Drug Design (2008 – present)
  • Associate Editor, New Biotechnology “Advances in Cell-free Protein Expression” (2010-2011)
  • BBSRC Biomolecular Sciences Grant Reviewer (2007 – present)
  • Cancer Research UK Reviewer (2004 - present)
  • MRC Grant Reviewer (2004 - present)
  • Wellcome Trust Grant Reviewer (2004 - present)
  • Director, Science Capital (2010-present)
  • Associate Professor, Department of Pharmacology, University of Colorado Health Sciences Center (2002-2003)
  • Assistant Professor, Department of Pharmacology, University of Colorado Health Sciences Center (1995-2002)
  • Postdoctoral Fellow, Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto (1993-1995)

Publications

Kiran, MR, SM Di Pietro, JM. Olson, GS Payne, M Overduin (2007) Solution structure of Sla1 Homology domain 1 and NPFxD motif recognition responsible for endocytic cargo internalisation, EMBO J, 26(7):1963-71

Kami, K, T Dafforn, M Chidgey, M Overduin (2009) The desmoglein specific cytoplasmic region is intrinsically disordered in solution, J Mol Biol, 386(2):531-43.
Knowles, TJ, R Finka, C Smith, YP Lin, T Dafforn, M Overduin (2009) Membrane proteins solubilized intact in lipid containing nanoparticles bounded by styrene maleic acid copolymer, J Amer Chem Soc, 131(22):7484-5.

Cao, X, Ü Coskun, SB Buschhorn, M Grzybek, M Roessle, TR Dafforn, M Lenoir, M Overduin, K Simons (2009) The Golgi protein FAPP2 tubulates membranes, PNAS USA 106(50):21121-21125.

Lenoir, M, Ü Coskun, M Grzybek, X Cao, SB Buschhorn, J James, K Simons, M Overduin, (2010) Structural basis of wedging the Golgi membrane by FAPP pleckstrin homology domains, EMBO R,11(4):279-84.

Rajesh, S. TJ Knowles, M Overduin (2011) Production of membrane proteins without cells or detergents, N Biotechnology 28(3):250-4.

Wolny MD, Grzybek M, Bok E, Chorzalska AD, Czogalla A, Lenoir M, Adamczyk K, Kolondra A, Diakowski W, Overduin M, Sikorski AF (2011) Key amino acid residues of ankyrin-sensitive phosphatidylethanolamine/ phosphatidylcholine-lipid binding site of βI–spectrin, PLoS One. 2011;6(6):e21538

Knowles, TJ, DF Browning, M Jeeves, R Maderbocus, S Rajesh, P Sridhar, E Manoli, D Emery, U Sommer, A Spencer, DL Leyton, D Squire, RR Chaudhuri, MR Viant, AF Cunningham, IR Henderson, M Overduin (2011) Structure and function of BamE within the outer membrane and the β-barrel assembly machine, EMBO R, 12(2):123-8.

Al-Jassar C, Knowles T, Jeeves M, Kami K, Bikker H, Overduin M, Chidgey M (2011) The nonlinear structure of the desmoplakin plakin domain and the effects of cardiomyopathy-linked mutations, J Mol Biol, 411(5):1049-61

Rajesh S, Bago R, Odintsova E, Muratov G, Sridhar P, Rajesh S, Overduin M, Berditchevski F (2011) Binding to  syntenin-1 defines a new mode of ubiquitin-based interactions regulated by phosphorylation, J Biol Chem. 286(45):39606-14.

Expertise

Biochemical mechanisms of signalling proteins; structural biology of cancer; genetic diseases and microbial secretion; discovery of biomolecular ligands; elucidation of interactions between proteins and membranes using biophysical methods, including magnetic resonance spectroscopy, use of lipid-polymer based nanoparticles for membrane protein drug discovery; supporting entrepreneurs and innovation

Alternative contact number available for this expert: contact the press office

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