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  • richardmitnick 12:18 pm on March 28, 2015 Permalink | Reply
    Tags: , Electron Microscopy,   

    From Scripps: “Team Breaks Imaging Barrier” 


    Scripps Research Institute

    March 30, 2015
    Madeline McCurry-Schmidt

    Advances in Electron Microscopy Could Aid Drug Design

    A team from the Carragher lab has imaged a protein complex at the highest resolution ever achieved with single particle cryo-electron microscopy. The image reveals individual molecules at 2.8 Å and is, to the researchers’ knowledge, the first published research using this technique that shows individual water molecules.

    Scientists at The Scripps Research Institute (TSRI) have broken a major barrier in structural imaging. Their study, published recently in the journal eLife, shows a protein complex at the highest resolution ever achieved with a standard technique called single particle cryo-electron microscopy.

    “The instruments and software are now so good that we do not know what the barriers are any more,” said Bridget Carragher, a professor at TSRI with a joint appointment at the New York Structural Biology Center.

    With single particle cryo-electron microscopy, scientists freeze a sample and then expose it to a beam of high-energy electrons. This excites electrons in the sample, allowing scientists to capture an image.

    While the technique has many practical advantages over other structural biology methods, scientists have so far not been able to reach resolutions more detailed than 3 Angstroms (one ten-billionth of a meter, marked with the symbol Å). At this resolution, some of the details of the structure that are important for guiding drug design are not discernable.

    The new study shows that reaching resolutions greater than 3 Å is possible using single particle cryo-electron microscopy. The imaged protein complex reveals individual molecules at 2.8 Å and is, to the researchers’ knowledge, the first time a paper has been published showing individual water molecules using this technique.

    Better Imaging, Better Drugs

    The scientists used a new type of electron microscope, called the FEI Titan Krios, and a new-generation camera, called a Gatan K2 Summit, to break the 3 Å barrier.

    Titan Krios

    Gatan K2 Summit

    The FEI Titan Krios is housed on TSRI’s La Jolla, California, campus. It has a higher energy electron source and a more stable platform than other types of electron microscopes. It also operates with software developed at TSRI through the National Resource for Automated Molecular Microscopy to find the best parts of a sample for imaging.

    The Gatan K2 Summit camera improves imaging by directly detecting electrons, instead of losing resolution by converting electrons to light. The camera can also capture a series of images, essentially a movie, giving scientists the ability to correct for movements in the specimen and make the images as sharp as possible.

    Revealing high-resolution details in a structure helps researchers develop new drugs to treat disease. Structures seen at greater than 3 Å might show vulnerabilities in a virus where drugs could bind, for example.

    “By seeing everything in more detail, you can design more effective drugs,” said Melody Campbell, a TSRI graduate student and co-first author of the new paper with David Veesler, previously a post-doctoral fellow at TSRI and now an assistant professor at the University of Washington.

    The advances in single particle cryo-electron microscopy also allow scientists to image more kinds of structures, more quickly. For many years, scientists have relied on a high-resolution imaging technique called X-ray crystallography. Although X-ray crystallography has led to many advances in drug design, figuring out how to grow a crystal can take years and not all structures can be crystallized.

    Electron microscopy does not require a crystal, however, and many projects take only weeks or months.

    In the new study, the researchers imaged a protein complex from a microbe called Thermoplasma acidophilum. This protein complex, called a proteasome, is also found in humans and is an important target for treating many types of cancer.

    The team spent several months setting up the instruments—since the FEI Titan Krios was new to the institute—and then they captured all the raw data over a single weekend. They then used computational programs to select the clearest images and refine them over several months to build a 3D model of the proteasome.

    “It was a relief to know we had finally done it,” said Campbell. “Now we hope other people can just hop on the microscope, use similar strategies and also get high-resolution structures.”

    In addition to Carragher, Campbell and Veesler, authors of the study, “2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20 S proteasome using cryo-electron microscopy,” were Anchi Cheng and Clinton S. Potter of the New York Structural Biology Center. For more information on the paper, see http://elifesciences.org/content/4/e06380.

    This research was supported by the National Institutes of Health’s National Institute of General Medical Sciences (grant GM103310), a FP7 Marie Curie IOF fellowship (273427) and an American Heart Association fellowship (14PRE18870036).

    See the full article here.

    Please help promote STEM in your local schools.

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    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

  • richardmitnick 3:31 pm on January 28, 2013 Permalink | Reply
    Tags: , , Electron Microscopy,   

    From PNNL Lab: “Seeing a Common Catalyst with New Eyes” 

    Chemical imaging microscope shows corrugated gamma-alumina surface
    January 2013
    Suraiya Farukhi
    Christine Sharp

    Results: Neither smooth nor disordered, gamma-alumina nanoparticles are corrugated with tiny pores inside, according to scientists at Pacific Northwest National Laboratory. Using a powerful transmission electron microscope, the team obtained ultrahigh-resolution images and chemical data about the particle’s surface. They found that the particles were covered with ridges made from a more open, yet symmetrical, arrangement of atoms. The open arrangement on the surfaces, notated as (110), covers 70% of the nanoparticle.

    The surface of the plate-like particles is far from smooth, according to a new transmission electron microscopy study conducted by Pacific Northwest National Laboratory and the FEI Company.

    By understanding the structure and function of tiny gamma-alumina particles, scientists are taking crucial steps to optimizing and realizing new useful properties for these materials. ‘If we can learn about the surfaces, then we can tailor them and make them more efficient in catalytic applications,’ said Dr. Libor Kovarik, who led the imaging study as part of PNNL’s Chemical Imaging Initiative.

    Why It Matters: Reducing refineries’ energy demands or car and truck emissions requires efficient catalysts on durable support materials. The supporting material must withstand severe temperature and pressure changes. Gamma-alumina has been studied extensively, but its atomic arrangement has not been established because of the challenge of getting a detailed view of this complex material. Accurately describing the atomic structure is crucial for understanding and taking advantage of the best properties of gamma-alumina.

    ‘Catalytic research demands this type of state-of-the-art chemical imaging research,’ said Dr. Charles Peden, a heterogeneous catalysis scientist who worked on the study, and an Associate Director of PNNL’s Institute for Integrated Catalysis. ‘Dr. Kovarik’s outstanding new images from this powerhouse microscope have yielded unprecedented new information about a catalyst material of enormous practical utility.'”

    See the full article here.

    Pacific Northwest National Laboratory (PNNL) is one of the United States Department of Energy National Laboratories, managed by the Department of Energy’s Office of Science. The main campus of the laboratory is in Richland, Washington.

    PNNL scientists conduct basic and applied research and development to strengthen U.S. scientific foundations for fundamental research and innovation; prevent and counter acts of terrorism through applied research in information analysis, cyber security, and the nonproliferation of weapons of mass destruction; increase the U.S. energy capacity and reduce dependence on imported oil; and reduce the effects of human activity on the environment. PNNL has been operated by Battelle Memorial Institute since 1965.


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  • richardmitnick 1:14 pm on January 17, 2013 Permalink | Reply
    Tags: , , Electron Microscopy   

    From Berkeley Lab: “New Key to Organism Complexity Identified” 

    Berkeley Lab

    Berkeley Scientists Find that a Critical Transcription Factor Co-exists in Two Distinct States

    January 17, 2013
    Lynn Yarris

    The enormously diverse complexity seen amongst individual species within the animal kingdom evolved from a surprisingly small gene pool. For example, mice effectively serve as medical research models because humans and mice share 80-percent of the same protein-coding genes.

    The ‘rearranged’ state of the lobe A (yellow) of the horseshoe-like TFIID transcription factor enables TFIID to bind with DNA (green) and start the process by which DNA is copied into RNA.

    The key to morphological and behavioral complexity, a growing body of scientific evidence suggests, is the regulation of gene expression by a family of DNA-binding proteins called ‘transcription factors.’ Now, a team of researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley has discovered the secret behind how one these critical transcription factors is able to perform – a split personality.

    Using a technique called single-particle cryo-electron microscopy, the team, which was led by biophysicist Eva Nogales, showed that the transcription factor known as ‘TFIID’ can co-exist in two distinct structural states.”

    two people
    Michael Cianfrocco and Eva Nogales used single-particle cryo-electron microscopy to learn how the TFIID transcription factor helps regulate of gene expression, a process critical to the growth, development, health and survival of all organisms. (Photo by Roy Kaltschmidt)

    See the full article here.

    A U.S. Department of Energy National Laboratory Operated by the University of California


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