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High Resolution Electron Microscopy

Rendering of a macrophage infected with HIV showing the disposition and distribution of the virus within the cell.
Project information

The 3D informatics for High Resolution Electron Microscopy project is analyzing the life sciences at nanometer scales. It includes the following efforts:

  • Researchers are examining data acquired from advanced microscopes that generate 3D data to provide new insights into the spatial relationships of sub-cellular mechanisms and a better understanding of systems biology. This work is being done in partnership with the National Cancer Institute Laboratory for Cell Biology.
  • Computer scientists are doing high performance computing on commercial grade graphics hardware (GPUs) to accurately align and average sub-volumes of data generated from transmission electron tomography to achieve super-resolution that can illuminate protein structures as small as 10-20 angstroms. Researchers have applied these methods to study the glycoprotein trimeric spikes found on HIV viruses as well as those found on influenza virions.
  • Through biomedical image analysis of data from ion-abrasion scanning electron microscopes, researchers are studying the mechanism by which cells infected with HIV communicate the virus to healthy cells, leading to better understanding of the disease's development. They are using these technologies to help fight cancer, influenza, HIV/AIDS, and other public health risks.

This work is joint with LHNCBC's Audiovisual Program and Development Branch.

Publications/Tools: 
Tran EE, Borgnia MJ, Kuybeda O, Schauder DM, Bartesaghi A, Frank GA, Sapiro G, Milne JL, Subramaniam S. Structural mechanism of trimeric HIV-1 envelope glycoprotein activation. PLoS Pathog. 2012;8(7):e1002797. doi: 10.1371/journal.ppat.1002797. Epub 2012 Jul 12.
Murphy GE, Lowekamp B, Zerfas PM, Chandler RJ, Narasimha R, Venditti CP, Subramaniam S. Ion-abrasion scanning electron microscopy reveals distorted liver mitochondrial morphology in murine methylmalonic acidemia. J Struct Biol. 2010 Aug;171(2):125-32. doi: 10.1016/j.jsb.2010.04.005. Epub 2010 Apr 23.
Chen D, Chittajallu DR, Passalis G, Kakadiaris IA. Computational tools for quantitative breast morphometry based on 3D scans. Ann Biomed Eng. 2010 May;38(5):1703-18. doi: 10.1007/s10439-010-9971-z. Epub 2010 Mar 19.
Bennett AE, Narayan K, Shi D, Hartnell LM, Gousset K, He H, Lowekamp BC, Yoo TS, Bliss D, Freed EO, Subramaniam S. Ion-abrasion scanning electron microscopy reveals surface-connected tubular conduits in HIV-infected macrophages. PLoS Pathog. 2009 Sep;5(9):e1000591. doi: 10.1371/journal.ppat.1000591. Epub 2009 Sep 25.
Felts RL, Bennett A, Shi D, Freed E, Lifson J, Lowekamp B, Yoo TS, Bliss D, Subramaniam S. 3D Imaging of HIV transmission and entry using electron tomography and ion-abrasion scanning electron microscopy. Three Dimensional Electron Microscopy: Technical Advances and Recent Breakthroughs in 3DEM. Gordon Research Conference; 2008 Jun 15-20; Lucca (Barga), Italy.

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