Bridget Carragher, PhD

  • Adjunct Professor of Biochemistry and Molecular Biophysics
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Overview

Bridget Carragher received her Ph.D. in Biophysics from the University of Chicago in 1987. She then 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 as the Director of the National Resource for Automated Molecular Microscopy (NRAMM), an NIH funded national biotechnology research resource. The focus of NRAMM is the development of automated imaging techniques for solving three-dimensional structures of macromolecular complexes using cryo-transmission electron microscopy (cryoEM). The overall goal is to develop new methods to improve the entire process, from specimen preparation to the generation of the final three-dimensional map. In 2007 Bridget co-founded a new company, NanoImaging Services, Inc., whose goal is to provide cryoEM and other microscopy services to the biopharmaceutical and biotechnology industry. She serves as Chief Operations Officer of NanoImaging Services. In 2015 Bridget moved her academic lab from The Scripps Research Institute to the New York Structural Biology Center where she now serves as Co-Director of the Simons Electron Microscopy Center and is an Adjunct Professor at Columbia University, BMB department.

Academic Appointments

  • Adjunct Professor of Biochemistry and Molecular Biophysics

Gender

  • Female

Credentials & Experience

Education & Training

  • PhD, 1987 Biophysics, University of Chicago

Research

For almost my entire career I have been involved in the development of streamlined and automated methods for EM aimed at improving both the quality of EM data as well as the accessibility of these techniques to the wider biological community. Over the past 16 years my colleague, Clinton S. Potter, and I have built the National Resource for Automated Molecular Microscopy (NRAMM) up from scratch into an internationally respected Resource that is acknowledged to lead the way in the development and application of automated technologies for EM and in providing training at all levels. NRAMM has contributed to over 280 papers since it began. Contributions to teaching and training activities have included individual student and post-doctoral supervision and mentoring, and the organization of many workshops and courses. Of note is the large biennial NRAMM training workshop that has earned an outstanding international reputation.

Research Interests

  • Automation
  • Cryo electron microscopy (cryoEM)
  • New technology
  • Protein structure

Grants

Ongoing Research Support

P41 GM103310 (Carragher) 05/01/17 – 03/31/22

NIH/NIGMS

National Resource for Automated Molecular Microscopy

The overall goal is to provide a Research Resource for high-throughput molecular microscopy using automation for data acquisition and processing.

Past Research Support

P50 GM073197-07 Stevens (PI) 0 9/30/2009 - 07/31/2015

JCIMPT-Complexes

The primary mission is to develop and disseminate novel and enabling methods and technologies that lead to the structure determination of human membrane proteins and their complexes. The goal of the TEM subproject is to develop an automated assay to image, select, and classify membrane protein complexes.

Role: Investigator

R01 GM095573-01 Carragher (PI) 09/30/2010 - 07/31/2015

A Helical Crystallization Pipeline for Membrane Protein Structure by TEM

This project aims to establish helical crystallization as a standard method to add to the armamentarium of approaches for determining the structure of these critically important macromolecular machines.

Role:Co-PI

R01 GM099678 (Carragher and Potter) 09/01/12-08/31/16

NIH/NIGMS

Continued Development and Maintenance of Appion Software

The objective is to provide support for the continued development and maintenance of the Appion software.

R01 GM103966-01 (Potter) 04/01/13-02/28/17

NIH/NIGMS

High Throughput EM Sample Preparation for Structural Biology

The objective is to develop a novel approach to TEM specimen preparation, incorporating miniaturization and small volume (picoliter to nanoliter) dispensing that will enable high throughput screening of negatively stained samples.

Selected Publications

Carragher B, Bluemke DA, Gabriel B, Potel MJ, Josephs R. Structural analysis of polymers of sickle cell hemoglobin. I. Sickle hemoglobin fibers. J Mol Biol. 1988;199(2):315-31.

Carragher B, Whittaker M, Milligan RA. Helical processing using PHOELIX. J Struct Biol. 1996;116(1):107-12.

Henderson R, Sali A, Baker ML, Carragher B, Devkota B, Downing KH, Egelman EH, Feng Z, Frank J, Grigorieff N, Jiang W, Ludtke SJ, Medalia O, Penczek PA, Rosenthal PB, Rossmann MG, Schmid MF, Schroder GF, Steven AC, Stokes DL, Westbrook JD, Wriggers W, Yang H, Young J, Berman HM, Chiu W, Kleywegt GJ, Lawson CL. Outcome of the first electron microscopy validation task force meeting. Structure. 2012;20(2):205-14. PMCID: 3328769.

Lander GC, 4Stagg SM, Voss NR, Cheng A, Fellmann D, Pulokas J, Yoshioka C, Irving C, Mulder A, Lau PW, Lyumkis D, Potter CS, Carragher B. Appion: an integrated, database-driven pipeline to facilitate EM image processing. J Struct Biol. 2009;166(1):95-102. PMCID: 2775544.

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. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science. 2013;342(6165):1484-90.

Marabini R, Carragher B, Chen S, Chen J, Cheng A, Downing KH, Frank J, Grassucci RA, Bernard Heymann J, Jiang W, Jonic S, Liao HY, Ludtke SJ, Patwari S, Piotrowski AL, Quintana A, Sorzano CO, Stahlberg H, Vargas J, Voss NR, Chiu W, Carazo JM. CTF Challenge: Result summary. J Struct Biol. 2015;190(3):348-59. PMCID: 4672951.

Moeller A, Kirchdoerfer RN, Potter CS, Carragher B, Wilson IA. Organization of the influenza virus replication machinery. Science. 2012;338(6114):1631-4. PMCID: PMC3578580.

Mulder AM, Yoshioka C, Beck AH, Bunner AE, Milligan RA, Potter CS, Carragher B, Williamson JR. Visualizing ribosome biogenesis: parallel assembly pathways for the 30S subunit. Science. 2010;330(6004):673-7. PMCID: PMC2990404.

Mulligan SK, Speir JA, Razinkov I, Cheng A, Crum J, Jain T, Duggan E, Liu E, Nolan JP, Carragher B, Potter CS. Multiplexed TEM Specimen Preparation and Analysis of Plasmonic Nanoparticles. Microsc Microanal. 2015;21(4):1017-25.

Patwardhan A, Carazo JM, Carragher B, Henderson R, Heymann JB, Hill E, Jensen GJ, Lagerstedt I, Lawson CL, Ludtke SJ, Mastronarde D, Moore WJ, Roseman A, Rosenthal P, Sorzano CO, Sanz-Garcia E, Scheres SH, Subramaniam S, Westbrook J, Winn M, Swedlow JR, Kleywegt GJ. Data management challenges in three-dimensional EM. Nat Struct Mol Biol. 2012;19(12):1203-7. PMCID: 4048199.

Potter CS, Pulokas J, Smith P, Suloway C, Carragher B. Robotic grid loading system for a transmission electron microscope. J Struct Biol. 2004;146(3):431-40.

Quispe J, Damiano J, Mick SE, Nackashi DP, Fellmann D, Ajero TG, Carragher B, Potter CS. An improved holey carbon film for cryo-electron microscopy. Microsc Microanal. 2007;13(5):365-71.

Razinkov I, Dandey VP, Wei H, Zhang Z, Melnekoff D, Rice WJ, Wigge C, Potter CS, Carragher B. A new method for vitrifying samples for cryoEM. J Struct Biol. 2016;195(2):190-8.

Stagg SM, Gurkan C, Fowler DM, LaPointe P, Foss TR, Potter CS, Carragher B, Balch WE. Structure of the Sec13/31 COPII coat cage. Nature. 2006;439(7073):234-8.

Suloway C, Pulokas J, Fellmann D, Cheng A, Guerra F, Quispe J, Stagg S, Potter CS, Carragher B. Automated molecular microscopy: the new Leginon system. J Struct Biol. 2005;151(1):41-60.4.

Zhu Y, Carragher B, Glaeser RM, Fellmann D, Bajaj C, Bern M, Mouche F, de Haas F, Hall RJ, Kriegman DJ, Ludtke SJ, Mallick SP, Penczek PA, Roseman AM, Sigworth FJ, Volkmann N, Potter CS. Automatic particle selection: results of a comparative study. J Struct Biol. 2004;145(1-2):3-14.