Beamline scientist for MASSIF-1


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  Beamline Scientist

Tel: +33(0)476207637





I am a scientist at the EMBL Grenoble Outstation and a visiting Scientist in the Structural Biology Group at the ESRF where I run MASSIF-1 the world leading beamline for fully automatic intelligent data collection. My research interests centre around synchrotron radiation methods development and instrumentation and combining multiple techniques, such as EM and SAXS, with high resolution X-ray crystallography and NMR to investigate the biological transfer of phosphate groups and membrane protein structure and function.


1. Automation of complex experiments in MX

The process of structure solution of biological macromolecules relies heavily on method development. Automation has played a key role in the solution of many important complexes and, at the ESRF, is changing the way MX experiments are performed.  Our research focuses on intelligent automation of sample handling, extraction of the best quality data and experimental feedback through advanced screening methods.  These developments come together in the new MX facility, MASSIF - the next generation of automated synchrotron beamlines for Structural Biology.


Selected references:

  • Nurizzo D, Bowler MW*,‡, Caserotto H, Dobias F, Giraud T, Surr J, Guichard N, Papp G, Guijarro M, Mueller-Dieckmann C, Flot D, McSweeney S, Cipriani F, Theveneau P, Leonard GA. (2016) RoboDiff: combining a sample changer and goniometer for highly automated macromolecular crystallography experiments. Acta Cryst. D72, 966-975.
  • Svensson, O., Monaco, S., Popov, A. N., Nurizzo, D. & Bowler, M. W. (2015). Fully automatic characterization and data collection from crystals of biological macromolecules, Acta Cryst. D71 1757-1767
  • Bowler M.W.,Nurizzo, D., et al. (2015) MASSIF-1: A beamline dedicated to the fully automatic characterisation and data collection from crystals of biological macromolecules J. Sync. Rad. 22 1540-1547
  • Bowler, M.G. and Bowler, M.W. (2014) Measurement of the intrinsic variability within protein crystals: implications for sample evaluation and data collection strategies, Acta Cryst. F70, 127-132
  • Bowler, M.W., Guijarro, M., Petitdemange, S., Baker, I., Svensson, O., Burghammer, M., Muller-Dieckmann, C., Gordon, E., Flot, D., McSweeney, S.M. and Leonard, G.A. (2010) Diffraction Cartography: applying microbeams to macromolecular crystallography sample evaluation and data collection. Acta Cryst. D66, 855-864


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2. The use and misuse of phosphoryl transfer in signalling networks and pathogenesis

Our work focusses on two aspects of the biological transfer of phosphate groups. First,  in collaboration with Prof. Jon Waltho (University of Sheffield, UK), we aim to determine the chemistry of this fundamental reaction and second we are working on how phosphoryl tranfer is used in signalling networks by both the cell itself and by pathogens, for the latter we collaborate with Dr. Ali Hakimi (Universite Grenoble-Alpes).  The transfer of phosphoryl groups is probably the most important enzyme-catalysed reaction in biology.  All organisms use phosphate in the form of ATP to store and transmit energy and phosphoryl transfer is also used to control processes as diverse as cell signalling, regulation of cellular division, membrane structure and enzyme function.  Consequently, a huge number of enzymes, up to 10% of the human genome, have evolved to catalyse phosphoryl transfer. Dissecting how these enzymes catalyse the reaction is of vital importance in understanding the cellular processes they regulate and perhaps designing drugs to target specific pathways. 


Selected references:

  • Pellegrini E, Palencia A, Braun L, Kapp U, Bougdour A, Belrhali H, Bowler MW, Hakimi MA. (2017) Structural Basis for the Subversion of MAP Kinase Signaling by an Intrinsically Disordered Parasite Secreted Agonist. Structure 25,16-26.      Access the recommendation on F1000Prime
  • Jin, Y., Bhattasali, D., Pellegrini, E., Forget, S.M., Baxter, N.J., Cliff, M.J., Webster, C.E., Bowler, M.W., Jakeman, D.L., Blackburn, G.M. and Waltho, J.P. (2014) α-Fluorophosphonates reveal how a phosphomutase conserves transition state conformation over hexose recognition in its two-step reaction Proc. Nat. Acad. Sci. USA. 111, 12384-12389
  • Griffin, J L., Bowler, M.W., Baxter, N.J., Leigh, K. N., Dannatt, H.R., Hounslow, A.M., Blackburn, G.M., Webster, C.E., Cliff, M.J. and Waltho, J.P. (2012) Near attack conformers dominate β-phosphoglucomutase complexes where geometry and charge distribution reflect those of substrate Proc. Nat. Acad. Sci. USA. 109, 6910-6915
  • Zerrad, L., Merli, A., Schroeder, G.F., Varga, A., Graczer, E., Pernot, P., Round, A., Vas, M. and Bowler, M.W. (2011) A spring loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase. J. Biol. Chem., 286, 14040-14048
  • Cliff, M.J., Bowler, M.W., Szabo, J., Marston, J.P., Varga, A., Hounslow, A.M., Baxter, N.J., Blackburn, G.M., Vas, M. and Waltho, J.P. (2010) Transition state analogue structures of human phosphoglycerate kinase reveal the dominance of charge balance in catalysis. J. Am. Chem. Soc., 132,  6507-16

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3. Crystal handling - dehydration and cryo cooling

We are working on developing new cryo-cooling methods and controlled dehydration of crystals to improving the diffraction characteristics (in collaboration with the instrumentation group at the EMBL, Grenoble). Our efforts are aimed at improving the reliabilty of th emethods and automating them as far as possible

Selected references:

  • Bowler MG, Bowler DR, Bowler MW. (2017) Raoult's law revisited: accurately predicting equilibrium relative humidity points for humidity control experiments. J Appl Cryst 50, 631-638.
  • Bowler, M.W., Mueller, U., Weiss, M.S., Sanchez-Weatherby, J., Sorensen, T., Thunnissen, M, Ursby, T., Gobbo, A., Russi, S., Bowler, M.G., Svensson, O. and Cipriani, F. (2015) Automation and experience of controlled crystal dehydration: results from the European synchrotron HC1 collaboration Cryst. Growth Des.  15, 1043-1054
  • Wheeler, M.J., Russi, S., Bowler, M.G. and Bowler, M.W. (2012) Measurement of the equilibrium relative humidity for common precipitant concentrations: facilitating controlled dehydration experiments Acta Cryst. F68, 111-114
  • Pellegrini, E., Piano, D. and Bowler, M.W. (2011) Direct cryocooling of naked crystals: Are cryoprotection agents always necessary? Acta Cryst. D67, 902-906


4. Membrane protein structure and function

We are working on the role membrane proteins play in the enormous resistance of the bacterium Deinococcus radiodurans (DR) to a variety of extreme conditions.  The first line of defense of prokaryotes to environmental shock are the surface layer (or S-layer) proteins of the outer membrane. In DR these proteins form hexagonal crystalline planes covering the outer membrane acting as protective layer with proposed roles as diverse as ion traps to that of an exoskeleton.  The S-layer has been studied extensively with a wealth of biochemical data and its macrostructure has been investigated by electron microscopy.  However, molecular details of its assembly and response to its environment remain unknown.  The S-layer protein from native D. radiodurans membranes has been purified and we are proceeding with structural studies.

We are also working on the ATP synthase from eubacteria, the central energy generating complex in all forms of life.  Using a combination of SAXS and X-ray crystallography we hope to gain greater insights into this large membrane bound molecular motor.


Selected references:

  • Farci, D., Bowler, M.W., Kirkpatrick, J., McSweeney, S., Tramontano, E. and Piano, D. (2014) New features of the cell wall of the radio-resistant bacterium Deinococcus radiodurans, BBA Biomembranes, 1838, 1978-1984
  • Bowler M. W., Montgomery M. G., Leslie, A. G. W and Walker, J. E. (2007). Ground state structure of F1-ATPase from bovine heart mitochondria at 1.9 Å  resolution. J. Biol. Chem. 282, 14238-14242
  • Bowler M. W., Montgomery M. G., Leslie, A. G. W and Walker, J. E. (2006). How azide inhibits ATP hydrolysis by the F-ATPases. Proc. Nat. Acad. Sci. USA. 103, 8646-8649
  • Kuo, A; Bowler, M. W.; Zimmer, J.; Antcliff, J. F. and Doyle, D. A. (2003).  Increasing the diffraction limit and internal order of a membrane protein crystal by dehydration.  J. Struct. Biol. 141, 97-102