The National Resource for Automated Molecular Microscopy (NRAMM) was established in December 2002 to develop, test and apply technology for automating structure determination of macromolecules by cryoelectron microscopy. During our initial startup period, we established some of the basic infrastructure and successfully demonstrated the power of automation applied to molecular microscopy. With our funding renewed in 2006 we focused on extending our technologies to provide a complete and integrated pipeline for the reconstruction of macromolecular machines. NRAMM's unique role has been to demonstrate both the possibility and the enormous potential of automation for molecular microscopy and show that it can be used in the service of compelling and challenging biological problems. We have also, in accordance with our original mission, used the infrastructure to open up the previously esoteric practices of EM structural biology to a much wider group of researchers including those whose main focus is nanotechnology and translational research. Our goals over the next 5 years are to further expand the possibilities of automation and continue to address the remaining limitations of molecular microscopy. To serve this mission we will focus on three Technological Research and Development Projects: (1) developing a novel approach to specimen preparation;(2) optimizing resolution and throughput;and (3) expanding our data processing pipeline to enable novel structural investigations of the most challenging macromolecules. These projects will be driven by, and interact very intensively with, 9 Driving Biological Projects, which represent a broad scope of biomedical research areas. We will also continue to serve the national community by providing support and access to the advanced technologies at NRAMM for a wide range of collaborative and service projects. Dissemination and Training activities will include the large international biennial NRAMM workshop, numerous smaller training and multi-disciplinary workshops, distribution and support of the major software infrastructure developed at NRAMM, and promoting the broader use of our technologies by making them widely known to the scientific community.

Public Health Relevance

Electron microscopy (EM) is now established as an essential tool for studying macromolecular machines that are central to cellular function, and thus has a basic and fundamental relevance for both the healthy and diseased states. This project will develop novel technologies that will increase both the pace and reach of EM structural studies, and will support fundamental research efforts in drug and vaccine development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103310-13
Application #
8636489
Study Section
Special Emphasis Panel (ZRG1-CB-J (40))
Program Officer
Wu, Mary Ann
Project Start
2002-09-30
Project End
2017-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
13
Fiscal Year
2014
Total Cost
$1,334,578
Indirect Cost
$558,054
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Piasecka, Anna; Czapinska, Honorata; Vielberg, Marie-Theres et al. (2017) The Y. bercovieri Anbu crystal structure sheds light on the evolution of highly (pseudo)symmetric multimers. J Mol Biol :
Yuan, Zuanning; Riera, Alberto; Bai, Lin et al. (2017) Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1. Nat Struct Mol Biol 24:316-324
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Chowdhury, Saikat; Carter, Joshua; Rollins, MaryClare F et al. (2017) Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex. Cell 169:47-57.e11
Han, Han; Monroe, Nicole; Sundquist, Wesley I et al. (2017) The AAA ATPase Vps4 binds ESCRT-III substrates through a repeating array of dipeptide-binding pockets. Elife 6:
Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui et al. (2017) Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex. Cell 171:414-426.e12
Liu, Qingbo; Acharya, Priyamvada; Dolan, Michael A et al. (2017) Corrigendum: Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer. Nat Struct Mol Biol 24:553

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