News Release: Research

Aug. 18,  2010

Advanced Electron Microscopes at Emory Showcase New Phase-Plate Technology

Cryo-electron instrument with phase-plate technology is one of only two in the United States

News Article ImageHIV: Isolated HIV-1 virion preserved by flash freezing and imaged by cryo-electron tomography. Scale bar = 100 nm. View larger graphic.

Emory University has acquired two state-of-the-art transmission electron microscopes (TEMs) to provide high-resolution images of viruses, bacteria, tissues and artificial biomaterials. The instruments will be located at the Robert P. Apkarian Integrated Electron Microscopy Core and are scheduled for delivery in August and September 2010.

The centerpiece of the expanded facility will be a 200 kV field emission TEM equipped with an energy filter, high resolution CCD camera, and the newly emerging Zernike phase plate technology. All of these advances combined on one instrument will enhance the ability of scientists from Emory and the entire Southeast to visualize cells, viruses and even the molecular machines inside cells in their native states, without the need for chemical fixation and stains that alter their structure. A limited number of electron microscopes have been equipped with phase plate technology: only a handful in the world and two in the United States so far.

The 200 kV instrument will be dedicated to cryo-imaging and analysis of biological and soft materials, says Elizabeth R. Wright, PhD, assistant professor of pediatrics at Emory University School of Medicine, director of the electron microscopy core, and a Georgia Research Alliance Distinguished Investigator. The new 120 kV TEM will be devoted to imaging sectioned and negatively stained samples. Both instruments were manufactured by JEOL Ltd. (Tokyo, Japan).

“With these instruments, in particular the 200 kV TEM, we can examine a much broader range of biological specimens at ‘macromolecular resolutions’ of 2 to 4 nm. This level of resolution allows us to visualize dramatic conformational changes that macromolecules within whole cells and viruses undergo during normal function,” Wright says. “We are excited about establishing Emory as a center for cryo-electron microscopy and looking forward to making these resources available to investigators at Emory and within the region.”

Caulobacter bacterial cells imaged without (left side) and with (right side) the Zernike phase contrast system
Caulobacter bacterial cells imaged without (left side) and with (right side)
the Zernike phase contrast system. View larger image.


Several decades ago, the development of phase contrast for optical microscopes allowed scientists to see living cells, which are normally transparent, without staining them. The development of optical phase contrast microscopy earned Frits Zernike the Nobel Prize in Physics in 1953. Kuniaki Nagayama’s group at the Okazaki Institute for Integrative Bioscience in Japan recently was able to overcome the technical obstacles to the use of phase contrast with electron microscopy, and Wright has participated in the evaluation of this new technology.

Wright’s research involves examining the three-dimensional structure of viruses, such as HIV-1 and paramyxoviruses, bacteria, and bacteriophages through cryo-electron microscopy. Her aim is to capture images of the viruses and bacteria and determine structural changes that lead to their infectious nature. This information is combined with biochemical and drug development studies to develop novel antimicrobials.

The 200kV instrument was acquired with the aid of a $1,050,000 grant from the National Science Foundation, with Wright as principal investigator.

The co-principal investigators are:

  • Vincent Conticello, PhD, professor of biomolecular chemistry at Emory University
  • Richard Compans, PhD, professor of microbiology and immunology at Emory University School of Medicine and director of the Emory Influenza Pathogenesis and Immunology Research Center
  • Paul Spearman, MD, chief research officer for Children’s Healthcare of Atlanta and vice chair of research for Emory University School of Medicine’s Department of Pediatrics
  • Eric Hunter, PhD, professor of pathology and laboratory medicine, co-director of the Emory Center for AIDS Research, and a Georgia Research Alliance Eminent Scholar.

A $500,000 grant from the National Center for Research Resources to Spearman, made under the American Recovery and Reinvestment Act, supported the acquisition of the 120 kV instrument.

Reference:
E.R Wright, J.B. Schooler, H.J. Ding, C. Kieffer, C. Fillmore, W.I. Sundquist, and G.J. Jensen. Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells. EMBO J. 26: 2218–2226 (2007).

Writer: Quinn Eastman

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