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For decades, pharma and biotech companies have enlisted sophisticated services to accelerate the discovery and development of novel drugs. Leading this modern-day revolution is cryo electron microscopy (cryo-EM). Since 2007, NIS has been a trail-blazing CRO providing cryo-EM services.
Diverse skill sets and state-of-the art technology, including more transmission electron microscopes than any provider in North America, help NIS make cryo-EM imaging and analysis accessible to companies of all sizes, and to teams across the drug discovery pipeline.
Through collaboration, learning, and a commitment to quality results, NIS helps our clients accelerate the development of new and life changing therapeutics.
NIS Achievements | Our Impact on Drug Discovery and More
150
+
3D structures determined by cryo-EM
76
%
of protein structures solved at 3.5 Å or better resolution
880
+
Virus, Vaccine and VLP projects completed
50
+
Structures solved by MicroED; Largest structure: 733 Da, Z’=4
200
+
AAV samples imaged; 3D structure of AAV solved to 1.8 Å
2,500
+
Liposomes & LNPs imaged
NIS has led the way since the earliest days of cryo-EM
Cryo-EM
NIS
1st 3D EM Gordon Conference is held to discuss the technology and biology related to using electron microscopy to understand molecular structures.
Bridget Carragher attends the first 3D EM Gordon Conference, along with the 3 scientists who would go on to win the Nobel prize for cryo-EM in 2017.
Henderson and colleagues showed for the first time that it is possible to obtain high-resolution structures of biomolecules using cryo-EM through averaging over many copies of the same object.1
1 Henderson, R., Baldwin, J. M., Ceska, T. A., Zemlin, F., Beckmann, E., and Downing, K. H. (1990) Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J. Mol. Biol. 213, 899-929
Clint Potter and Bridget Carragher start the Imaging Technology Group at the Beckman Institute at UIUC.
First Leginon paper published – describing a system to automatically acquire cryo-electron micrographs.2
2 Potter CS, Chu H, Frey B, Green C, Kisseberth N, Madden TJ, Miller KL, Nahrstedt K, Pulokas J, Reilein A, Tcheng D, Weber D, Carragher B. Leginon: a system for fully automated acquisition of 1000 electron micrographs a day. Ultramicroscopy. 1999 Jul;77(3-4):153-61. doi: 10.1016/s0304-3991(99)00043-1.
Bridget and Clint move from the Beckman Institute to Scripps, start the National Resource for Automated Molecular Microscopy (NRAMM).
Electron Microscopy Data Bank (EMDB) is launched to create a public archive of single particle reconstructions.
Maximum-likelihood 3D software to classify images from heterogenous single particles advances approach to computational sorting.3
3Scheres, S., Gao, H., Valle, M. et al. Disentangling conformational states of macromolecules in 3D-EM through likelihood optimization. Nat Methods4, 27–29 (2007). https://doi.org/10.1038/nmeth992
NanoImaging Services is founded by Bridget Carragher and Clint Potter, both researchers and professors at the Scripps Research Institute, to help improve access to the emerging power of Transmission Electron Microscopy (TEM).
New Direct Electron Detectors are developed.4, 5, 6, 7
4 Brilot AF, Chen JZ, Cheng A, Pan J, Harrison SC, Potter CS, Carragher B, Henderson R, Grigorieff N. Beam-induced motion of vitrified specimen on holey carbon film. J Struct Biol. 2012 Mar;177(3):630-7. doi: 10.1016/j.jsb.2012.02.003. Epub 2012 Feb 16.
5 Campbell, M.G., et al., Movies of ice-embedded particles enhance resolution in electron cryo-microscopy. Structure, 2012. 20(11): p. 1823-8. https://doi.org/10.1016/j.str.2012.08.026
6Veesler D, Campbell MG, Cheng A, Fu CY, Murez Z, Johnson JE, Potter CS, Carragher B. Maximizing the potential of electron cryomicroscopy data collected using direct detectors. J Struct Biol. 2013 Nov;184(2):193-202. doi: 10.1016/j.jsb.2013.09.003. Epub 2013 Sep 12.
7 Campbell, M.G., Veesler, D., Cheng, A., Potter, C.S. & Carragher, B. eLife 4, e06380 (2015). https://doi.org/10.7554/eLife.06380
Spotiton technology developed to improve vitrification.8
8 Jain T, Sheehan P, Crum J, Carragher B, Potter CS. Spotiton: a prototype for an integrated inkjet dispense and vitrification system for cryo-TEM. J Struct Biol. 2012;179(1):68-75. doi:10.1016/j.jsb.2012.04.020
NIS exclusively licenses Spotiton technology.
Structure of dual-variable-domain immunoglobulin molecules alone and bound to antigen on the cover of mAbs.9
9Ivan Correia, Joyce Sung, Randall Burton, Clarissa G. Jakob, Bridget Carragher, Tariq Ghayur & Czeslaw Radziejewski (2013) The structure of dual-variable-domain immunoglobulin molecules alone and bound to antigen, mAbs, 5:3, 364-372, DOI: 10.4161/mabs.24258
NIS expands into new facilities.
Publication of work originally done in 2007 for Merck: Characterization of virus-like particles in GARDASIL® by cryo transmission electron microscopy.10
10 Qinjian Zhao, Clinton S Potter, Bridget Carragher, Gabriel Lander, Jaime Sworen, Victoria Towne, Dicky Abraham, Paul Duncan, Michael W Washabaugh & Robert D Sitrin (2014) Characterization of virus-like particles in GARDASIL® by cryo transmission electron microscopy, Human Vaccines & Immunotherapeutics, 10:3, 734-739, DOI: https://www.tandfonline.com/doi/full/10.4161/hv.27316
Kulbrandt coins the term “resolution revolution” heralding “the beginning of a new era in molecular biology, where structures at near-atomic resolution are no longer the prerogative of x-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy.”11
NIS contributes to a study demonstrating the utility of TEM as "an effective orthogonal method to characterize protein aggregates...[providing] detailed information on the microstructure of the aggregates and...insights into the conformational integrity of the component proteins.12
12Sung JJ, Pardeshi NN, Mulder AM, Mulligan SK, Quispe J, On K, Carragher B, Potter CS, Carpenter JF, and Schneemann A. 2015. Transmission electron microscopy as an orthogonal method to characterize protein aggregates. J Pharm Sci. 104(2):750-59. doi: 10.1002/jps.24157. PMCID: 4376473.
3D structure of glutamate dehydrogenase (334 kDa) reported, breaks the 2 Å barrier with a resolution of 1.8 Å.13
13 Merk A, Bartesaghi A, Banerjee S, et al. Breaking cryo-EM resolution barriers to facilitate drug discovery. Cell. 2016;165:1698–1707. doi: https://doi.org/10.1016/j.cell.2016.05.040
Nobel Prize in Chemistry awarded to Jacques Dubochet, Joachim Frank and Richard Henderson “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution.”
The number of cryo-EM structures better than 4 Å in the EMDB demonstrating exponential growth.14
NIS solves a sub 2 Å structure of AAV.
Two papers publish the structure of apoferritin, a highly symmetric protein often used as a benchmark to push cryo-EM to its limits, at a record-breaking resolution of 1.2 Å, the first time that cryo-EM has achieved fully atomic resolution in a protein15 the second team reported a 1.25 Å structure16
15Nakane, T., Kotecha, A., Sente, A. et al. Single-particle cryo-EM at atomic resolution. Nature 587, 152–156 (2020). https://doi.org/10.1038/s41586-020-2829-0
16 Yip, K.M., Fischer, N., Paknia, E. et al. Atomic-resolution protein structure determination by cryo-EM. Nature 587, 157–161 (2020). https://doi.org/10.1038/s41586-020-2833-4
Novavax reports the development of a SARS-CoV-2 subunit vaccine, using cryo-EM images from NIS.17
17 Tian, JH., Patel, N., Haupt, R. et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun12, 372 (2021). https://doi.org/10.1038/s41467-020-20653-8
NIS East facility opens, just north of Boston, adding a second Glacios to the company's growing fleet of microscopes.
NIS West expands with the addition of a new building and NIS’s second Titan Krios microscope.
AlphaFold computational method offers “highly accurate protein structure prediction.”18
18 Jumper, J., Evans, R., Pritzel, A. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021). https://doi.org/10.1038/s41586-021-03819-2
$1.2M SBIR I/II Grant for development of microED workflows awarded.
NIS solves its 100th protein structure.
A second Glacios microscope is added at NIS-EAST.
NIS publishes two papers describing our newly developed MicroED structure determination pipeline and automated data collection software. 19 20
19 J. F. Bruhn, G. Scapin, A. Cheng, B. Q. Mercado, D. G. Waterman, T. Ganesh, S. Dallakyan, B. N. Read, T. Nieusma, K. W. Lucier, M. L. Mayer, N. J. Chiang, N. Poweleit, P. T. McGilvray, T. S. Wilson, M. Mashore, C. Hennessy, S. Thomson, B. Wang, C. S. Potter, B. Carragher, Small Molecule Microcrystal Electron Diffraction for the Pharmaceutical Industry–Lessons Learned From Examining Over Fifty Samples. Frontiers Mol Biosci. 8, 648603 (2021). https://doi.org/10.3389/fmolb.2021.648603
20 A. Cheng, C. Negro, J. F. Bruhn, W. J. Rice, S. Dallakyan, E. T. Eng, D. G. Waterman, C. S. Potter, B. Carragher, Leginon: New features and applications. Protein Sci. 30, 136–150 (2021). https://doi.org/10.1002/pro.3967
NIS celebrates its 15-year anniversary.
Modular capsid decoration boosts adenovirus vaccine-induced humoral and cellular immunity against SARS-CoV-2.21
21 Modular capsid decoration boosts adenovirus vaccine-induced humoral and cellular immunity against SARS-CoV-2 Matthew D. J. Dicks, Louisa M. Rose, Lesley A. H. Bowman, Carl Graham, Katie J. Doores, Michael H. Malim, Simon J. Draper, Mark Howarth, Sumi Biswas bioRxiv 2022.02.20.480711; doi: https://www.biorxiv.org/content/10.1101/2022.02.20.480711v1
