Nikolaus Grigorieff

Nikolaus Grigorieff
Known forCryogenic Electron Microscopy (Cryo-EM)
SpouseMaria Gianferrari
Scientific career
FieldsStructural biology, biophysics
InstitutionsUMass Chan Medical School

Janelia Research Campus (2013-2018)

Brandeis University (1999-2013)
Websitehttps://grigoriefflab.umassmed.edu/

Nikolaus Grigorieff is a structural biologist and biophysicist and professor at the University of Massachusetts Chan Medical School, where he is a member of the RNA Therapeutics Institute.[1] He is also an investigator of the Howard Hughes Medical Institute (HHMI)[2] and a member of the United States National Academy of Sciences. His research focuses on determining the three-dimensional structures of proteins and macromolecular assemblies using high-resolution cryogenic electron microscopy (cryo-EM), as well as the development of computational methods for cryo-EM image processing.

Academic career

Grigorieff earned his M.S. in semiconductor physics in 1990[3] and Ph.D. in cryo-EM in 1993, both from the University of Bristol (UK), where he conducted thesis research with David Cherns focused on semiconductor devices and their analysis with the electron microscope (EM).[4] He subsequently completed postdoctoral training at the Medical Research Council in Cambridge (UK) with Richard Henderson on 2D crystals of bacteriorhodopsin.[5] Grigorieff started his own lab at Brandeis University in 1999 as assistant professor, promoted to associate professor in 2004, and Full Professor in 2006. He became an HHMI investigator in 2000.[2][6]

In 2013, Grigorieff moved his lab to Janelia Research Campus,[7] and then to UMass Chan Medical School in 2018 where he became a professor in the RNA Therapeutics Institute. Dr. Grigorieff has over 30,300 citations on Google Scholar.[8]

Research contributions

Grigorieff's laboratory studies the structure and function of proteins and protein complexes using cryo-EM. His work has addressed large macromolecular assemblies associated with RNA biology, including the spliceosome and the ribosome[9][10] with collaborator Andrei A. Korostelev and others, as well as membrane proteins such as ion channels and receptors. His research has also examined helical filaments, including microtubules and amyloid structures.[11]

In addition to structural studies, Grigorieff has contributed to the development of computational and methodological advances in cryo-EM, including CTFFIND5,[12] Frealign,[13] cisTEM,[14][15] Unblur,[16] all designed as open-source software. He played a role in advancing the use of dose-fractionated “movie” recording in cryo-EM to correct for beam-induced motion, a methodological improvement that contributed to significant gains in achievable resolution in the field.[17][18]

More recently, in collaboration with researchers at the Janelia Research Campus, he has worked on the development of an in situ cryo-EM approach known as two-dimensional template matching (2DTM).[19] This method is designed to enable the detection and localization of macromolecules within cellular cryo-EM images. Ongoing work in his laboratory includes applications of 2DTM for evaluating sample integrity, visualizing ligand–protein interactions, extending cryo-EM methods to smaller molecular complexes, and analyzing conformational variability in solution.[20]

Awards and honors

  • Research fellowship from the Humboldt Foundation (2004–2005)[21]
  • Paper of the Year Award, Journal of Structural Biology (2015)[22]
  • Election to the National Academy of Sciences, USA (2021)[23]

References

  1. ^ "RNA Therapeutics Institute Faculty". UMass Chan Medical School. 2021-12-13. Retrieved 2026-02-23.
  2. ^ a b "Nikolaus Grigorieff, PhD | Investigator | 2018-Present". www.hhmi.org. Retrieved 2026-02-23.
  3. ^ Grigorieff, N. (1990). Investigation of the Tungsten-aluminium Interface of VLSI Multi-level Interconnects by TEM, EDX and EELS. scholar.google.com (MSc thesis). University of Bristol. Retrieved 2026-02-25.
  4. ^ Grigorieff, N.; Cherns, D.; Yates, M. J.; Hockly, M.; Perrin, S. D.; Aylett, M. R. (1993-07-01). "Electron microscopy of ultra-thin buried layers in InP and InGaAs". Philosophical Magazine A. 68 (1): 121–136. Bibcode:1993PMagA..68..121G. doi:10.1080/01418619308219361. ISSN 0141-8610.
  5. ^ Grigorieff, N.; Ceska, T. A.; Downing, K. H.; Baldwin, J. M.; Henderson, R. (1996-06-14). "Electron-crystallographic Refinement of the Structure of Bacteriorhodopsin". Journal of Molecular Biology. 259 (3): 393–421. doi:10.1006/jmbi.1996.0328. ISSN 0022-2836. PMID 8676377.
  6. ^ "SBGrid Consortium - Tales - Nikolaus Grigorieff - HHMI's Janelia Research Campus". sbgrid.org. Retrieved 2026-02-25.
  7. ^ "Scientific Community Draws New Lab Heads to Janelia Farm Research Campus | HHMI". www.hhmi.org. Retrieved 2026-02-23.
  8. ^ "Nikolaus Grigorieff". scholar.google.com. Retrieved 2026-02-23.
  9. ^ Serrano, Antonio; Puerner, Charles; Chevalier, Louis; Plumb, Emily; Elferich, Johannes; Diggs, Stephen; Sinn, Ludwig Roman; Grigorieff, Nikolaus; Ralser, Markus; Delarue, Morgan; Bassilana, Martine; Arkowitz, Robert Alan (2025). "Decreased cytoplasmic crowding via inhibition of ribosome biogenesis can trigger Candida albicans filamentous growth". Nature Microbiology. 11 (1): 169–179. doi:10.1038/s41564-025-02205-2. ISSN 2058-5276. PMID 41372638.
  10. ^ Zottig, Ximena; Huang, Chun-Ying; Seraj, Zahra; Grigorieff, Nikolaus; Korostelev, Andrei A. (2025-12-29). "Structural basis for non-AUG translation regulation by 5MPs". bioRxiv 10.64898/2025.12.28.696766.
  11. ^ Liberta, Falk; Loerch, Sarah; Rennegarbe, Matthies; Schierhorn, Angelika; Westermark, Per; Westermark, Gunilla T.; Grigorieff, Nikolaus; Fändrich, Marcus; Schmidt, Matthias (2019). "Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids". Nature Communications. 10 (1) 1104. Bibcode:2019NatCo..10.1104L. bioRxiv 10.1101/357129. doi:10.1038/s41467-019-09033-z. PMC 6405766. PMID 30846696.
  12. ^ Elferich, Johannes; Kong, Lingli; Zottig, Ximena; Grigorieff, Nikolaus (2024-12-20). "CTFFIND5 provides improved insight into quality, tilt, and thickness of TEM samples". eLife. 13 RP97227. doi:10.7554/eLife.97227. ISSN 2050-084X. PMC 11661789. PMID 39704651.
  13. ^ "Frealign | The Grigorieff Lab". grigoriefflab.umassmed.edu. Retrieved 2026-02-23.
  14. ^ "Welcome to: | cisTEM". cistem.org. Retrieved 2026-02-23.
  15. ^ Grant, Timothy; Rohou, Alexis; Grigorieff, Nikolaus (2018-03-07). "cisTEM, user-friendly software for single-particle image processing". eLife. 7 e35383. Bibcode:2018eLife...735383G. doi:10.7554/eLife.35383. ISSN 2050-084X. PMC 5854467. PMID 29513216.
  16. ^ "Unblur & Summovie | The Grigorieff Lab". grigoriefflab.umassmed.edu. Retrieved 2026-02-23.
  17. ^ Campbell, Melody G.; Cheng, Anchi; Brilot, Axel F.; Moeller, Arne; Lyumkis, Dmitry; Veesler, David; Pan, Junhua; Harrison, Stephen C.; Potter, Clinton S.; Carragher, Bridget; Grigorieff, Nikolaus (2012-11-07). "Movies of ice-embedded particles enhance resolution in electron cryo-microscopy". Structure. 20 (11): 1823–1828. doi:10.1016/j.str.2012.08.026. ISSN 1878-4186. PMC 3510009. PMID 23022349.
  18. ^ Brilot, Axel F.; Chen, James Z.; Cheng, Anchi; Pan, Junhua; Harrison, Stephen C.; Potter, Clinton S.; Carragher, Bridget; Henderson, Richard; Grigorieff, Nikolaus (2012-03-01). "Beam-induced motion of vitrified specimen on holey carbon film". Journal of Structural Biology. 177 (3): 630–637. doi:10.1016/j.jsb.2012.02.003. ISSN 1095-8657. PMC 3322646. PMID 22366277.
  19. ^ Lucas, Bronwyn A.; Himes, Benjamin A.; Grigorieff, Nikolaus (2023-11-27). "Baited reconstruction with 2D template matching for high-resolution structure determination in vitro and in vivo without template bias". eLife. 12 RP90486. doi:10.7554/eLife.90486. PMC 10681363. PMID 38010355.
  20. ^ Zhang, Kexin; Grant, Timothy; Grigorieff, Nikolaus (2025-09-16). "Improved cryo-EM reconstruction of sub-50 kDa complexes using 2D template matching". bioRxiv 10.1101/2025.09.11.675606.
  21. ^ "Singleview". www.humboldt-foundation.de. Retrieved 2026-02-23.
  22. ^ "Paper of the Year Award". Journal of Structural Biology. 189 (3): 161–162. 2015-03-01. doi:10.1016/j.jsb.2015.01.006. ISSN 1047-8477.
  23. ^ "Nikolaus Grigorieff – NAS". National Academies of Science. Retrieved 2026-02-24.
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