Bridget Carragher

Bridget Olivia Carragher (born 17 June 1957, in South Africa) is an American physicist and a pioneer in electron microscopy. She is an Adjunct Professor at the Columbia University (New York City, NY), and together with Clint Potter the director of the National Resource for Automated Molecular Microscopy (NRAMM), director of the Simons Electron Microscopy Center at New York Structural Biology Center (New York City, NY) and PI at the National Center for CryoEM Access and Training. She is also Founder and Chief Operations Officer of the company NanoImaging Services, Inc.

Bridget Carragher
Born17 June 1957
CitizenshipUSA
Alma materUniversity of the Witwatersrand, Johannesburg, S. Africa (B.Sc. and M.Sc. in Physics)

Northwestern University, Evanston, Illinois (M.Sc. in Physics)

University of Chicago, Chicago, Illinois (Ph.D.)
Scientific career
FieldsElectron Microscopy, Structural Biology

Personal life

Carragher was born and grew up in South Africa. Except for a short period, where she lived in Ghana during her childhood and for a one-year period in England, she moved to the US after her master's degree and has lived there since. Carragher is an American citizen, is married and has two children.

Education

Carragher received her first education at the University of the Witwatersrand, South Africa, in the field of Physics (B.Sc.: 1975-1977; B.Sc. Hons: 1978-1978; M.Sc.: 1979-1981). In 1982 she graduated from the Northwestern University, Evanston, Illinois (M.Sc. in Physics). In the same year, she started her PhD at University of Chicago, Chicago, Illinois defending in 1987.

Career

For almost her entire career, Carragher has been involved in the development of streamlined and automated methods for electron microscopy (EM), aimed at improving both the quality of EM data as well as the accessibility of these techniques to the wider biological community. Her scientific career is a massive mixture of professional experience and activities.

After her PhD, Carragher worked in a variety of positions, both in industry and academia until moving to the Scripps Research Institute in 2001. Since 2002 she has served, together with Clint Potter, as the Director of the National Resource for Automated Molecular Microscopy (NRAMM), an NIH funded national biotechnology research resource. The purpose of the NRAMM is to lead the way in the development and application of automated technologies for EM and in providing training at all levels.

In 2007 Carragher co-founded a new company, NanoImaging Services, Inc., where she serves as Chief Operations Officer. The company's goal is to provide cryoEM and other microscopy services to the biopharmaceutical and biotechnology industry.

In 2015 Carragher and Clint moved their academic lab from The Scripps Research Institute to the New York Structural Biology Center where they serve as Co-Directors of the Simons Electron Microscopy Center. In May 2018 they were awarded a U24 grant to start the National Center for CryoEM Access and Training (NCCAT).

Positions and Employment
Year Position
1987 - 1988 Research Associate, U. Chicago
1988 - 1990 Senior Scientist, CEMAX Incorporated, Santa Clara, California
1990 - 1991 Assistant Research Neuroscientist, Dept. of Neuroscience, UCSD
1992 - 1998 Director, Optical Visualization Facility, Beckman Institute, UIUC
1994 - 2001 Adjunct Assistant Professor, Dept. of Cell and Structural Biology, UIUC
1996 - 1999 Senior Research Scientist, National Center for Supercomputing Applications, UIUC
1998 - 2001 Director, Imaging Technology Group, Beckman Institute, UIUC
2001 - 2012 Associate Professor, Dept. of Cell Biology, The Scripps Research Institute. La Jolla, CA
2003–present Director, National Resource for Automated Molecular Microcopy (NRAMM)
2007–present Founder and Chief Science Officer, NanoImaging Services, Inc.
2012 - 2014 Professor, Dept. of Integrative Structural and Computational Biology, The Scripps Research Institute. La Jolla, CA
2015–present Director, Simons Electron Microscopy Center, New York Structural Biology Center, NY, NY
2015–present Adjunct Professor, Columbia University, New York, NY
2018–present Co-PI, National Center for CryoEM Access and Training
Other Experience and Professional Memberships
Year Activity
1993–present Editorial Board, Journal of Structural Biology
1993–present Member of various NIH/NSF Study Sections
1993 - 2000 Scientific Advisory Committee, National Center for Macromolecular Imaging, Baylor College of Medicine
1993, 1995 Co-organizer, Workshop on Advanced Computing for Biological Imaging, UIUC/NCSA
1995 Co-organizer, A Hands-on Workshop on Practical Stereological Techniques, UIUC
1995–present Member of Advisory Committee, HVEM Resource, Boulder, Co.
1996 Co-editor, Journal of Structural Biology Special Issue on “Software Resources for Image Processing and Visualization in Structural Biology”
1998–present Member of Advisory Committee, BMIRR, Wadsworth Center, Albany, NY
1997, 1999 Vice-chair, Chair, Gordon Conference on 3DEM of Macromolecules
2003 Co-organizer, Multidisciplinary Workshop on Automated Particle Selection
2003 - 2014 Co-organizer, Biennial Workshop In Molecular Microscopy
2003 Co-Editor, Journal of Structural Biology, Special Issues on Automated Particle Selection and Analytical Methods
2003 - 2005 NIH BBCB Study Section
2005 - 2007 NIH MI Study Section
2005–present Associate Editor, Journal of Structural Biology
2011 - 2015 Scientific Advisory Committee, Transcontinental EM Initiative for Membrane Protein Structure
2012 - 2014 Advisory Board, National Canadian CryoEM Facility
2013 - 2015 External Advisory Committee, Theoretical and Computational Biophysics Group
2014–present Chair, EMDB Committee for cryoEM map challenge
2015–present Member, wwPDB Integrative/Hybrid Method (IHM) Task Force: Federation Subgroup
2015–present Member, Diamond Scientific Advisory Committee
2015–present Member, RCSB Protein Data Bank Advisory Committee
2015–present Member, External Advisory Board, National Center for X-ray Tomography
2016–present Editorial Board, Cell Chemical Biology
2017–present Member, NCXT Advisory Committee
2017–present Member, International Scientific Advisory Board, Max Planck Institute, Frankfurt
2017–present External Advisory Board, UTSW multi-user cryoEM facility
2017 Honorary Fellow of the Royal Microscopy Society
2017–present Editorial Board, Biophysical Journal
2018–present External Advisory Board, Harvard multi-user cryoEM facility

Contribution to Science

During her career, Carragher published over 150 papers (165 currently), received several research funding grantsand owns five patentsso far.

Patents
  • Smith PE, Callahan MP, Daniel I, Potter CS, Carragher B, Suloway CJ, inventors; Robotic system for sequencing multiple specimens between a holding tray and microscope. 2005, US 2005/0107917 A1.
  • Mulder A, Carragher B, Potter CS, inventors; Characterization of particulates using electron microscopy and image processing methods. 2011, Provisional. Filed 8/17/2011.
  • Carragher B, Potter CS, Jain T, inventors; Preparation of specimen arrays on an EM grid. 2012, Provisional. Filed 1/17/2012.
  • Carragher B, Potter CS, Jain T, inventors; Superhydrophilic specimen grids for electron microscopy. 2012, Provisional. Filed 1/17/2012.
  • Carragher B, Potter CS, Jain T, Kahn P, Wiktor P, inventors; Apparatus and method for producing specimens for electron microscopy. 2012, Provisional. Filed 1/17/2012.

Five most significant contributions to the EM field
  1. Suloway, C; Pulokas, J; Fellmann, D; Cheng, A; Guerra, F; Quispe, J; Stagg, S; Potter, CS; Carragher, B (2005). "Automated molecular microscopy: the new Leginon system". J Struct Biol. 151 (1): 41–60. doi:10.1016/j.jsb.2005.03.010. PMID 15890530.
  2. Lander, GC; Stagg, SM; Voss, NR; Cheng, A; Fellmann, D; Pulokas, J; Yoshioka, C; Irving, C; Mulder, A; Lau, PW; Lyumkis, D; Potter, CS; Carragher, B (2009). "Appion: an integrated, database-driven pipeline to facilitate EM image processing". J Struct Biol. 166 (1): 95–102. doi:10.1016/j.jsb.2009.01.002. PMC 2775544. PMID 19263523.
  3. Lyumkis, D; Julien, JP; de Val, N; Cupo, A; Potter, CS; Klasse, PJ; Burton, DR; Sanders, RW; Moore, JP; Carragher, B; Wilson, IA; Ward, AB (2013). "Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer". Science. 342 (6165): 1484–90. doi:10.1126/science.1245627. PMC 3954647. PMID 24179160.
  4. Noble, AJ; Wei, H; Dandey, VP; Zhang, Z; Tan, YZ; Potter, CS; Carragher, B (2018). "Reducing effects of particle adsorption to the air-water interface in cryo-EM". Nat Methods.
  5. Scapin, G; Dandey, VP; Zhang, Z; Prosise, W; Hruza, A; Kelly, T; Mayhood, T; Strickland, C; Potter, CS; Carragher, B (2018). "Structure of the insulin receptor-insulin complex by single-particle cryo-EM analysis". Nature. 556 (7699): 122–5. doi:10.1038/nature26153. PMC 5886813. PMID 29512653.

Additional selected contributions to the EM field

CryoEM automation

Carragher was an early advocate for automated methods for electron microscopy. She developed software to analyze poorly ordered sickle cell hemoglobin fibers[1] and went on to collaborate with Ron Milligan's group to develop a pipeline for helical processing (Phoelix).[2] Together with Clint Potter, Carragher then led the development of Leginon,[3] a system for automated control and data acquisition from an electron microscope, and Appion,[4] a pipeline for single particle data processing. Recently they showed that they could use this automated pipeline to obtain maps to a resolution of 2.8 Å.

New technologies for TEM

Carragher and her team have developed a number of novel technologies for transmission electron microscopy (TEM). These include Spotiton, an inkjet dispense and vitrification system for cryo-TEM,[5][6] robotic devices to load TEM specimens into the microscope,[7] liquid handling robots for controlling sample vitrification[8][9] and negative staining, and new substrates, including one that led to grids that are now commercially available under the trade name Cflats.[10]

Contributions to structural biology

The major goals of technology development have been driven by the needs of compelling biological research projects. These are normally managed by a graduate student or post-doctoral fellow who establishes close lines of communication between the EM group and the biological research lab. While their major role is to manage the technical efforts, they are often also intimately involved in guiding the biological questions and writing the papers. The first authors of these papers[11][12][13][14] were all either graduate students or post-docs in Carragher's labs.

Contributions to the field:

Carragher has been involved in a number of efforts to validate and improve methods for the entire field. These include a particle picking workshop,[15] the recent CTF challenge[16] and a number of workshops organized by the EMDB to discuss standards and validation.[17][18] She have also organized numerous workshops, including the well-regarded NRAMM biennial Advanced Methods Workshop that is attended by ≈150 participants.

References
  1. Carragher, B.; Bluemke, D. A.; Gabriel, B.; Potel, M. J.; Josephs, R. (1988-01-20). "Structural analysis of polymers of sickle cell hemoglobin. I. Sickle hemoglobin fibers". Journal of Molecular Biology. 199 (2): 315–331. doi:10.1016/0022-2836(88)90316-6. ISSN 0022-2836. PMID 3351926.
  2. Carragher, B.; Whittaker, M.; Milligan, R. A. (January 1996). "Helical processing using PHOELIX". Journal of Structural Biology. 116 (1): 107–112. doi:10.1006/jsbi.1996.0018. ISSN 1047-8477. PMID 8742731.
  3. Suloway, Christian; Pulokas, James; Fellmann, Denis; Cheng, Anchi; Guerra, Francisco; Quispe, Joel; Stagg, Scott; Potter, Clinton S.; Carragher, Bridget (July 2005). "Automated molecular microscopy: the new Leginon system". Journal of Structural Biology. 151 (1): 41–60. doi:10.1016/j.jsb.2005.03.010. ISSN 1047-8477. PMID 15890530.
  4. Lander, Gabriel C.; Stagg, Scott M.; Voss, Neil R.; Cheng, Anchi; Fellmann, Denis; Pulokas, James; Yoshioka, Craig; Irving, Christopher; Mulder, Anke (April 2009). "Appion: an integrated, database-driven pipeline to facilitate EM image processing". Journal of Structural Biology. 166 (1): 95–102. doi:10.1016/j.jsb.2009.01.002. ISSN 1047-8477. PMC 2775544. PMID 19263523.
  5. Jain, Tilak; Sheehan, Patrick; Crum, John; Carragher, Bridget; Potter, Clinton S. (July 2012). "Spotiton: A prototype for an integrated inkjet dispense and vitrification system for cryo-TEM". Journal of Structural Biology. 179 (1): 68–75. doi:10.1016/j.jsb.2012.04.020. PMC 3378829. PMID 22569522.
  6. Dandey, Venkata P.; Wei, Hui; Zhang, Zhening; Tan, Yong Zi; Acharya, Priyamvada; Eng, Edward T.; Rice, William J.; Kahn, Peter A.; Potter, Clinton S.; Carragher, Bridget (May 2018). "Spotiton: New features and applications". Journal of Structural Biology. 202 (2): 161–169. doi:10.1016/j.jsb.2018.01.002. PMC 6317895. PMID 29366716.
  7. Potter, Clinton S.; Pulokas, James; Smith, Paul; Suloway, Christian; Carragher, Bridget (June 2004). "Robotic grid loading system for a transmission electron microscope". Journal of Structural Biology. 146 (3): 431–440. doi:10.1016/j.jsb.2004.02.002. ISSN 1047-8477. PMID 15099584.
  8. Quispe, Joel; Damiano, John; Mick, Stephen E.; Nackashi, David P.; Fellmann, Denis; Ajero, Teddy G.; Carragher, Bridget; Potter, Clinton S. (October 2007). "An improved holey carbon film for cryo-electron microscopy". Microscopy and Microanalysis. 13 (5): 365–371. Bibcode:2007MiMic..13..365Q. doi:10.1017/S1431927607070791. ISSN 1431-9276. PMID 17900388.
  9. Mulligan, Sean K.; Speir, Jeffrey A.; Razinkov, Ivan; Cheng, Anchi; Crum, John; Jain, Tilak; Duggan, Erika; Liu, Er; Nolan, John P. (August 2015). "Multiplexed TEM Specimen Preparation and Analysis of Plasmonic Nanoparticles". Microscopy and Microanalysis. 21 (4): 1017–1025. Bibcode:2015MiMic..21.1017M. doi:10.1017/S1431927615014324. ISSN 1435-8115. PMC 4701052. PMID 26223550.
  10. Razinkov, Ivan; Dandey, Venkat; Wei, Hui; Zhang, Zhening; Melnekoff, David; Rice, William J.; Wigge, Christoph; Potter, Clinton S.; Carragher, Bridget (August 2016). "A new method for vitrifying samples for cryoEM". Journal of Structural Biology. 195 (2): 190–198. doi:10.1016/j.jsb.2016.06.001. ISSN 1095-8657. PMC 5464370. PMID 27288865.
  11. Stagg, Scott M.; Gürkan, Cemal; Fowler, Douglas M.; LaPointe, Paul; Foss, Ted R.; Potter, Clinton S.; Carragher, Bridget; Balch, William E. (2006-01-12). "Structure of the Sec13/31 COPII coat cage". Nature. 439 (7073): 234–238. Bibcode:2006Natur.439..234S. doi:10.1038/nature04339. ISSN 1476-4687. PMID 16407955.
  12. Mulder, Anke M.; Yoshioka, Craig; Beck, Andrea H.; Bunner, Anne E.; Milligan, Ronald A.; Potter, Clinton S.; Carragher, Bridget; Williamson, James R. (2010-10-29). "Visualizing Ribosome Biogenesis: Parallel Assembly Pathways for 30S Subunit". Science. 330 (6004): 673–677. Bibcode:2010Sci...330..673M. doi:10.1126/science.1193220. ISSN 0036-8075. PMC 2990404. PMID 21030658.
  13. Moeller, Arne; Kirchdoerfer, Robert N.; Potter, Clinton S.; Carragher, Bridget; Wilson, Ian A. (2012-12-21). "Organization of the Influenza Virus Replication Machinery". Science. 338 (6114): 1631–1634. Bibcode:2012Sci...338.1631M. doi:10.1126/science.1227270. ISSN 0036-8075. PMC 3578580. PMID 23180774.
  14. Lyumkis, Dmitry; Julien, Jean-Philippe; de Val, Natalia; Cupo, Albert; Potter, Clinton S.; Klasse, Per-Johan; Burton, Dennis R.; Sanders, Rogier W.; Moore, John P. (2013-12-20). "Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer". Science. 342 (6165): 1484–1490. Bibcode:2013Sci...342.1484L. doi:10.1126/science.1245627. ISSN 1095-9203. PMC 3954647. PMID 24179160.
  15. Zhu, Yuanxin; Carragher, Bridget; Glaeser, Robert M.; Fellmann, Denis; Bajaj, Chandrajit; Bern, Marshall; Mouche, Fabrice; de Haas, Felix; Hall, Richard J. (January 2004). "Automatic particle selection: results of a comparative study". Journal of Structural Biology. 145 (1–2): 3–14. CiteSeerX 10.1.1.5.9218. doi:10.1016/j.jsb.2003.09.033. ISSN 1047-8477. PMID 15065668.
  16. Marabini, Roberto; Carragher, Bridget; Chen, Shaoxia; Chen, James; Cheng, Anchi; Downing, Kenneth H.; Frank, Joachim; Grassucci, Robert A.; Heymann, J. Bernard (June 2015). "CTF Challenge: Result Summary". Journal of Structural Biology. 190 (3): 348–359. doi:10.1016/j.jsb.2015.04.003. ISSN 1047-8477. PMC 4672951. PMID 25913484.
  17. Henderson, Richard; Sali, Andrej; Baker, Matthew L.; Carragher, Bridget; Devkota, Batsal; Downing, Kenneth H.; Egelman, Edward H.; Feng, Zukang; Frank, Joachim (2012-02-08). "Outcome of the First Electron Microscopy Validation Task Force Meeting". Structure. 20-330 (2): 205–214. doi:10.1016/j.str.2011.12.014. ISSN 0969-2126. PMC 3328769. PMID 22325770.
  18. Patwardhan, Ardan; Carazo, José-Maria; Carragher, Bridget; Henderson, Richard; Heymann, J Bernard; Hill, Emma; Jensen, Grant J; Lagerstedt, Ingvar; Lawson, Catherine L (December 2012). "Data management challenges in three-dimensional EM". Nature Structural & Molecular Biology. 19 (12): 1203–1207. doi:10.1038/nsmb.2426. ISSN 1545-9993. PMC 4048199. PMID 23211764.
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