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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: 
KC S, Alam M, Roy P, Wendling L, Antani SK, Thoma GR. A simple and efficient arrowhead detection in biomedical images. International J Pattern Recognition and Artificial Intelligence (IJPRAI), 30(5), 1657002, 2016, DOI: 10.1142/S0218001416570020.
Do T, Murphy G, Earl LA, Del Prete GQ, Grandinetti G, Li GH, Estes JD, Rao P, Trubey CM, Thomas J, Spector J, Bliss D, Nath A, Lifson JD, Subramaniam S. Three-dimensional imaging of HIV-1 virological synapses reveals membrane architectures involved in virus transmission. J Virol. 2014 Sep;88(18):10327-39. doi: 10.1128/JVI.00788-14. Epub 2014 Jun 25.
Narayan K, Danielson CM, Lagarec K, Lowekamp BC, Coffman P, Laquerre A, Phaneuf MW, Hope TJ, Subramaniam S. Multi-resolution correlative focused ion beam scanning electron microscopy: applications to cell biology. J Struct Biol. 2014 Mar;185(3):278-84. doi: 10.1016/j.jsb.2013.11.008. Epub 2013 Dec 1.
Schauder DM, Kuybeda O, Zhang J, Klymko K, Bartesaghi A, Borgnia MJ, Mayer ML, Subramaniam S. Glutamate receptor desensitization is mediated by changes in quaternary structure of the ligand binding domain. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5921-6. doi: 10.1073/pnas.1217549110. Epub 2013 Mar 25.
Harris AK, Meyerson JR, Matsuoka Y, Kuybeda O, Moran A, Bliss D, Das SR, Yewdell JW, Sapiro G, Subbarao K, Subramaniam S. Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4592-7. doi: 10.1073/pnas.1214913110. Epub 2013 Mar 4.
Tran EEH, Kuybeda O, Bartesaghi A, Milne JLS, Subramaniam S. Binding of Neutralizing Antibodies Results in Distinct Quaternary Conformations of Trimeric HIV-1 Envelope Glycoproteins. Biophysical Society 57th Annual Meeting; 2013 Feb 2-6; Philadelphia.
Kuybeda O, Frank GA, Bartesaghi A, Borgnia M, Subramaniam S, Sapiro G. A collaborative framework for 3D alignment and classification of heterogeneous subvolumes in cryo-electron tomography. J Struct Biol. 2013 Feb;181(2):116-27. doi: 10.1016/j.jsb.2012.10.010. Epub 2012 Oct 27.
Harris AK, Meyerson JR, Matsuoka Y, Kuybeda O, Moran A , Bliss D, Das SR, Yewdell J, Sapiro G, Subbarao K, Subramaniam S. Molecular Structures of Native HA Trimers on 2009 H1N1 Pandemic Influenza Virus Complexed with Neutralizing Antibodies. Biophysical Journal. 2013 Jan 29;104(2 Supp 1):414a. 57th Annual Meeting of the Biophysical Society; 2013 Feb 2-6; Philadelphia. DOI: http://dx.doi.org/10.1016/j.bpj.2012.11.2310.
Meyerson JR, Tran EE, Kuybeda O, Chen W, Dimitrov DS, Gorlani A, Verrips T, Lifson JD, Subramaniam S. Molecular structures of trimeric HIV-1 Env in complex with small antibody derivatives. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):513-8. doi: 10.1073/pnas.1214810110. Epub 2012 Dec 24.
Yoo TS, Bliss D, Lowekamp B, Chen D, Murphy GE, Narayan K, Hartnell LM, Do T, Subramaniam S. Visualizing cells and humans in 3D: Biomedical image analysis at nanometer and meter scales. IEEE Computer Graphics and Applications. 2012 Sep-Oct;32(5):39-49. DOI: 10.1109/MCG.2012.68.

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