The Harvard Center for Cryo-Electron Microscopy (HC2EM) is a joint effort by Harvard Medical School, Dana-Farber Cancer Institute, Boston Children’s Hospital, and Massachusetts General Hospital to provide state-of-the-art cryo-EM instrumentation and expertise for the Harvard structural biology community. This user facility offers consultation and training by staff in specimen preparation, microscope operation, image acquisition, and data analysis. 

Additionally, the Molecular Electron Microscopy Suite (MEMS) at Harvard Medical School is a separate user resource currently available to qualified researchers. This user facility offers training and supervision in negative-stain and cryo-transmission electron microscopy. Equipment includes three transmission electron microscopes, two cryo plungers, and sample preparation areas. 

We are looking for a CryoET Specialist to join the team.

HC2EM staff

Click for more details on how to apply!

Recent Publications

Martin Filipovski, Jelly H. M. Soffers, Seychelle M. Vos, and Lucas Farnung. 6/16/2022. “Structural basis of nucleosome retention during transcription elongation.” Science, 376, 6599, Pp. 1313-1316. Publisher's VersionAbstract
In eukaryotes, RNA polymerase (Pol) II transcribes chromatin and must move past nucleosomes, often resulting in nucleosome displacement. How Pol II unwraps the DNA from nucleosomes to allow transcription and how DNA rewraps to retain nucleosomes has been unclear. Here, we report the 3.0-angstrom cryo–electron microscopy structure of a mammalian Pol II-DSIF-SPT6-PAF1c-TFIIS-nucleosome complex stalled 54 base pairs within the nucleosome. The structure provides a mechanistic basis for nucleosome retention during transcription elongation where upstream DNA emerging from the Pol II cleft has rewrapped the proximal side of the nucleosome. The structure uncovers a direct role for Pol II and transcription elongation factors in nucleosome retention and explains how nucleosomes are retained to prevent the disruption of chromatin structure across actively transcribed genes. Eukaryotic cells organize their large genomes into a compacted structure called chromatin. The condensed structure of chromatin, with its fundamental unit the nucleosome, represents a challenge to nucleic acid–transacting machines including RNA polymerase II (Pol II), the enzyme responsible for the transcription of most protein-coding genes. How RNA Pol II overcomes nucleosomes without disrupting chromatin organization remains unknown. Using cryo–electron microscopy, Filipovski et al. provided structural snapshots of a complex between mammalian RNA Pol II and a nucleosome that show how previously transcribed DNA rewraps the nucleosome. The finding provides a structural basis of how nucleosomes, and consequently epigenetic marks, are retained during transcription. —DJ A high-resolution cryo–electron microscopy structure explains how nucleosomes are retained to prevent disruption of chromatin across actively transcribed genes.
Nils Marechal, Banyuhay P. Serrano, Xinyan Zhang, and Charles J. Weitz. 5/2/2022. “Formation of thyroid hormone revealed by a cryo-EM structure of native bovine thyroglobulin.” Nature Communications, 13, 1, Pp. 2380. Publisher's VersionAbstract
Thyroid hormones are essential regulators of metabolism, development, and growth. They are formed from pairs of iodinated tyrosine residues within the precursor thyroglobulin (TG), a 660-kDa homodimer of the thyroid gland, by an oxidative coupling reaction. Tyrosine pairs that give rise to thyroid hormones have been assigned within the structure of human TG, but the process of hormone formation is poorly understood. Here we report a \textasciitilde3.3-\AA cryo-EM structure of native bovine TG with nascent thyroid hormone formed at one of the predicted hormonogenic sites. Local structural rearrangements provide insight into mechanisms underlying thyroid hormone formation and stabilization.
Di Liu, François A. Thélot, Joseph A. Piccirilli, Maofu Liao, and Peng Yin. 5/2/2022. “Sub-3-Å cryo-EM structure of RNA enabled by engineered homomeric self-assembly.” Nature Methods. Publisher's VersionAbstract
High-resolution structural studies are essential for understanding the folding and function of diverse RNAs. Herein, we present a nanoarchitectural engineering strategy for efficient structural determination of RNA-only structures using single-particle cryogenic electron microscopy (cryo-EM). This strategy–-ROCK (RNA oligomerization-enabled cryo-EM via installing kissing loops)–-involves installing kissing-loop sequences onto the functionally nonessential stems of RNAs for homomeric self-assembly into closed rings with multiplied molecular weights and mitigated structural flexibility. ROCK enables cryo-EM reconstruction of the Tetrahymena group I intron at 2.98-\AA resolution overall (2.85þinspace}\AA for the core), allowing de novo model building of the complete RNA, including the previously unknown peripheral domains. ROCK is further applied to two smaller RNAs–-the Azoarcus group I intron and the FMN riboswitch, revealing the conformational change of the former and the bound ligand in the latter. ROCK holds promise to greatly facilitate the use of cryo-EM in RNA structural studies.

Recent News


A Better Look: The development of cryo-EM has revolutionized structural biology

September 12, 2018
"Throughout history, observations of structure, from Hooke’s cells to the beaks of Darwin’s finches, have provided insights necessary to understand how life works. This is particularly true in structural biology, a discipline focused on visualizing life at its most fundamental. Discoveries of the atomic structures of important proteins and biological molecules have been among the most celebrated in science and have generated more than a dozen Nobel Prizes, new fields of research, and multibillion-dollar companies."

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