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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-CB-J (40))
Program Officer
Wu, Mary Ann
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Scripps Research Institute
La Jolla
United States
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Campbell, Melody G; Underbakke, Eric S; Potter, Clinton S et al. (2014) Single-particle EM reveals the higher-order domain architecture of soluble guanylate cyclase. Proc Natl Acad Sci U S A 111:2960-5
Campbell, Melody G; Kearney, Bradley M; Cheng, Anchi et al. (2014) Near-atomic resolution reconstructions using a mid-range electron microscope operated at 200 kV. J Struct Biol 188:183-7
Butan, Carmen; Filman, David J; Hogle, James M (2014) Cryo-electron microscopy reconstruction shows poliovirus 135S particles poised for membrane interaction and RNA release. J Virol 88:1758-70
Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten et al. (2014) Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity 40:669-80
Majzoub, Ramsey N; Chan, Chia-Ling; Ewert, Kai K et al. (2014) Uptake and transfection efficiency of PEGylated cationic liposome-DNA complexes with and without RGD-tagging. Biomaterials 35:4996-5005
Friesen, Robert H E; Lee, Peter S; Stoop, Esther J M et al. (2014) A common solution to group 2 influenza virus neutralization. Proc Natl Acad Sci U S A 111:445-50
Veesler, David; Cupelli, Karolina; Burger, Markus et al. (2014) Single-particle EM reveals plasticity of interactions between the adenovirus penton base and integrin ?V?3. Proc Natl Acad Sci U S A 111:8815-9
Nolan, John P; Duggan, Erika; Condello, Danilo (2014) Optimization of SERS tag intensity, binding footprint, and emittance. Bioconjug Chem 25:1233-42
Parent, Kristin N; Erb, Marcella L; Cardone, Giovanni et al. (2014) OmpA and OmpC are critical host factors for bacteriophage Sf6 entry in Shigella. Mol Microbiol 92:47-60
Campbell, Melody G; Smith, Brian C; Potter, Clinton S et al. (2014) Molecular architecture of mammalian nitric oxide synthases. Proc Natl Acad Sci U S A 111:E3614-23

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