General Lab Information

Sean McSweeney

Photon Division Management, National Synchrotron Light Source II

Sean McSweeney

Brookhaven National Laboratory

National Synchrotron Light Source II
Bldg. 745
P.O. Box 5000
Upton, NY 11973-5000

(631) 344-4506
smcsweeney@bnl.gov

The underlying theme of Sean's managerial and research interests has been to find methods to make best use of synchrotron lightsources in general, and in particular to reveal the complexity of biological systems, and make these methods accessible to the broadest possible community. The latest manefestation of these interests can be seen in the life sciences at NSLS-II and for cryogenic electron microscopy, he recently initiated a new program for imaging biological systems (links on the right).

Sean has constructed and operated x-ray beamlines for macromolecular crystallography at synchrotron sites since 1991. Initially developing methods for the routine use of anomalous dispersion in the elucidation of macromolecular structure. He has made significant contributions to the automation of synchrotron beamlines and the understanding of the fundamental processes occurring when intense x-ray beams meet macromolecular crystals. He continues efforts in this area  with the goal of providing increasingly automated and reliable macromolecular structure determination facilities whilst dealing with the issues of “real” samples.
 

Expertise | Education | Publications


Expertise

  •  Structural Biology at Synchrotron Facilities.The scientific community using the lightsource is skilled in the molecular biology and cellular biology techniques necessary for the production of crystals and the interpretation of the structure in a biological context, but usually not in x-ray optics and instrumentation. The major innovation of Sean's work, and the part of the teams he has led, is in making accessible the complex x-ray tools in a cost effective fashion. 

  •  Automation of Crystallographic Experiments.The automation of MX experiment requires the automation of photon delivery and preparation; the automation of sample handling under cryogenic conditions; the alignment of the sample to the x-ray beam; initial diffraction assessment and planning of the beamlines and finally the evaluation of the data being collected. Having this suite of automation tools in place has been a monumental effort coordinated among many scientists.

  • Phasing of Macromolecular Structures. One of the difficulties of resolving the structures of macromolecules is the "phase problem:" a fundamental issue with the diffraction experiment in which the measurement of the intensities in the diffraction pattern results in the loss of the phases that are necessary for the mathematical reconstruction of the molecule. Synchrotron radiation experiments in the 1980's by Hendrickson and collaborators demonstrated the possibility of using the unique spectra properties of x-ray beams to resolve this problem, however, both the experiment and the problem of reconstruction remained a considerable difficulty. The combined efforts of many groups lead to the simplification of the protocols and ultimately the anomalous scattering method becoming the structure determination method of choice. 

Education

  • PhD Physical Chemistry, Unversity of Manchester, UK. 1991
  • BSc Chemistry and Physics Joint Hons, Unversity of Manchester, UK. 1986

Selected Publications

  • Chai J, Cai Y, Pang C, Wang L, McSweeney S, Shanklin J, Liu Q (2021) Structural basis for SARS-CoV-2 envelope protein recognition of human cell junction protein PALS1. Nature Communications. doi: 10.1038/s41467-021-23533-x
  • Ebrahim A, Riley BT, Kumaran D, Andi B, Fuchs MR, McSweeney S, Keedy DA (2021) The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro). doi: 10.1101/2021.05.03.437411
  • McSweeney DM, McSweeney SM, Liu Q (2020) A self-supervised workflow for particle picking in cryo-EM. IUCrJ 7:719–727. doi: 10.1107/s2052252520007241
  • Takemaru L, Guo G, Zhu P, Hendrickson WA, McSweeney S, Liu Q (2020) PyMDA: microcrystal data assembly using Python. Journal of Applied Crystallography 53:277–281. doi: 10.1107/s160057671901673x
  • Zhu P, Yu X-H, Wang C, Zhang Q, Liu W, McSweeney S, Shanklin J, Lam E, Liu Q (2020) Structural Basis for Ca2+-Dependent Activation of a Plant Metacaspase. doi: 10.1101/2020.03.09.983940
  • Li X, Lin Y, Liu Q, McSweeney S, Yoo S (2019) Picking Particles in Cryo-EM Micrographs without Knowing the Particle Size. 2019 New York Scientific Data Summit (NYSDS). doi: 10.1109/nysds.2019.8909792
  • Fuchs MR, Shi W, Gao Y, Andi B, Jakoncic J, Lazo EO, Soares A, Myers SF, Skinner J, Liu Q, Bernstein HJ, Nazaretski E, McSweeney S (2019) Ultra-fast raster-scanning synchrotron serial micro-crystallography. Acta Crystallographica Section A Foundations and Advances 75:e23–e23. doi: 10.1107/s2053273319095330
  • Guo G, Zhu P, Fuchs MR, Shi W, Andi B, Gao Y, Hendrickson WA, McSweeney S, Liu Q (2019) Synchrotron microcrystal native-SAD phasing at a low energy. IUCrJ 6:532–542. doi: 10.1107/s2052252519004536
  • Oscarsson M, Beteva A, Flot D, Gordon E, Guijarro M, et al. (2019) MXCuBE2: the dawn of MXCuBE Collaboration. Journal of Synchrotron Radiation 26:393–405. doi: 10.1107/s1600577519001267
  • Liu Q, Guo G, Zhu P, Fuchs MR, Shi W, Andi B, Gao Y, Hendrickson WA, McSweeney S (2019) Data analysis for synchrotron microcrystal native-SAD phasing. Acta Crystallographica Section A Foundations and Advances 75:a230–a230. doi: 10.1107/s0108767319097733
  • Skubák P, Araç D, Bowler MW, Correia AR, Hoelz A, Larsen S, Leonard GA, McCarthy AA, McSweeney S, Mueller-Dieckmann C, Otten H, Salzman G, Pannu NS (2018) A new MR-SAD algorithm for the automatic building of protein models from low-resolution X-ray data and a poor starting model. IUCrJ 5:166–171. doi: 10.1107/s2052252517017961
  • 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 Crystallographica Section D Structural Biology 72:966–975. doi: 10.1107/s205979831601158x
  • Bowler MW, Nurizzo D, Barrett R, Beteva A, Bodin M, Caserotto H, Delagenière S, Dobias F, Flot D, Giraud T, Guichard N, Guijarro M, Lentini M, Leonard GA, McSweeney S, Oskarsson M, Schmidt W, Snigirev A, von Stetten D, Surr J, Svensson O, Theveneau P, Mueller-Dieckmann C (2015) MASSIF-1: a beamline dedicated to the fully automatic characterization and data collection from crystals of biological macromolecules. Journal of Synchrotron Radiation 22:1540–1547. doi: 10.1107/s1600577515016604
  • Round A, Felisaz F, Fodinger L, Gobbo A, Huet J, Villard C, Blanchet CE, Pernot P, McSweeney S, Roessle M, Svergun DI, Cipriani F (2015) BioSAXS Sample Changer: a robotic sample changer for rapid and reliable high-throughput X-ray solution scattering experiments. Acta Crystallographica Section D Biological Crystallography 71:67–75. doi: 10.1107/s1399004714026959
  • De Maria Antolinos A, Pernot P, Brennich ME, Kieffer J, Bowler MW, Delageniere S, Ohlsson S, Malbet Monaco S, Ashton A, Franke D, Svergun D, McSweeney S, Gordon E, Round A (2015) ISPyB for BioSAXS, the gateway to user autonomy in solution scattering experiments. Acta Crystallographica Section D Biological Crystallography 71:76–85. doi: 10.1107/s1399004714019609
  • Sarre A, Ökvist M, Klar T, Hall DR, Smalås AO, McSweeney S, Timmins J, Moe E (2015) Structural and functional characterization of two unusual endonuclease III enzymes from Deinococcus radiodurans. Journal of Structural Biology 191:87–99. doi: 10.1016/j.jsb.2015.05.009
  • Farci D, Bowler MW, Kirkpatrick J, McSweeney S, Tramontano E, Piano D (2014) New features of the cell wall of the radio-resistant bacterium Deinococcus radiodurans. Biochimica et Biophysica Acta (BBA) - Biomembranes 1838:1978–1984. doi: 10.1016/j.bbamem.2014.02.014
  • Stelter M, Acajjaoui S, McSweeney S, Timmins J (2013) Structural and Mechanistic Insight into DNA Unwinding by Deinococcus radiodurans UvrD. PLoS ONE 8:e77364. doi: 10.1371/journal.pone.0077364
  • Radzimanowski J, Dehez F, Round A, Bidon-Chanal A, McSweeney S, Timmins J (2013) An "open" structure of the RecOR complex supports ssDNA binding within the core of the complex. Nucleic Acids Research 41:7972–7986. doi: 10.1093/nar/gkt572
  • McSweeney S (2013) Searching for Needles in Haystacks: Automation and the Task of Crystal Structure Determination. NATO Science for Peace and Security Series A: Chemistry and Biology 47–57. doi: 10.1007/978-94-007-6232-9_5
  • Fisher SJ, Blakeley MP, Cianci M, McSweeney S, Helliwell JR (2012) Protonation-state determination in proteins using high-resolution X-ray crystallography: effects of resolution and completeness. Acta Crystallographica Section D Biological Crystallography 68:800–809. doi: 10.1107/s0907444912012589
  • Moe E, Hall DR, Leiros I, Monsen VT, Timmins J, McSweeney S (2012) Structure–function studies of an unusual 3-methyladenine DNA glycosylase II (AlkA) fromDeinococcus radiodurans. Acta Crystallographica Section D Biological Crystallography 68:703–712. doi: 10.1107/s090744491200947x
  • Giordano R, Leal RMF, Bourenkov GP, McSweeney S, Popov AN (2012) The application of hierarchical cluster analysis to the selection of isomorphous crystals. Acta Crystallographica Section D Biological Crystallography 68:649–658. doi: 10.1107/s0907444912006841
  • Pellegrino S, Radzimanowski J, de Sanctis D, Erba EB, McSweeney S, Timmins J (2012) Structural and Functional Characterization of an SMC-like Protein RecN: New Insights into Double-Strand Break Repair. Structure 20:2076–2089. doi: 10.1016/j.str.2012.09.010
  • Delageniere S, Brenchereau P, Launer L, Ashton AW, Leal R, Veyrier S, Gabadinho J, Gordon EJ, Jones SD, Levik KE, McSweeney SM, Monaco S, Nanao M, Spruce D, Svensson O, Walsh MA, Leonard GA (2011) ISPyB: an information management system for synchrotron macromolecular crystallography. Bioinformatics 27:3186–3192. doi: 10.1093/bioinformatics/btr535
  • Gabadinho J, Beteva A, Guijarro M, Rey-Bakaikoa V, Spruce D, Bowler MW, Brockhauser S, Flot D, Gordon EJ, Hall DR, Lavault B, McCarthy AA, McCarthy J, Mitchell E, Monaco S, Mueller-Dieckmann C, Nurizzo D, Ravelli RBG, Thibault X, Walsh MA, Leonard GA, McSweeney SM (2010) MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments. Journal of Synchrotron Radiation 17:700–707. doi: 10.1107/s0909049510020005
  • Bowler MW, Guijarro M, Petitdemange S, Baker I, Svensson O, Burghammer M, Mueller-Dieckmann C, Gordon EJ, Flot D, McSweeney SM, Leonard GA (2010) Diffraction cartography: applying microbeams to macromolecular crystallography sample evaluation and data collection. Acta Crystallographica Section D Biological Crystallography 66:855–864. doi: 10.1107/s0907444910019591
  • Timmins J, Gordon E, Caria S, Leonard G, Acajjaoui S, Kuo M-S, Monchois V, McSweeney S (2009) Structural and Mutational Analyses of Deinococcus radiodurans UvrA2 Provide Insight into DNA Binding and Damage Recognition by UvrAs. Structure 17:547–558. doi: 10.1016/j.str.2009.02.008
Sean McSweeney

Brookhaven National Laboratory

National Synchrotron Light Source II
Bldg. 745
P.O. Box 5000
Upton, NY 11973-5000

(631) 344-4506
smcsweeney@bnl.gov

Sean's Links