The overall mission of our research program is to understand the structure and function of complex biological assemblies by combining novel technologies for 3D biological imaging with advanced methods for image segmentation and computational analysis. We take an interdisciplinary approach to this problem, using emerging technologies in cryo-electron microscopy as our primary tool. Members of our group work on different, yet, complementary aspects of structural analysis. Key areas of current and future focus are:(i) the development and application of novel technologies for three-dimensional electron microscopy of specimens ranging in size from small molecules to tissues, (ii) determination of the dynamic architectures of cellular structures involved in cell division and chemotaxis in bacterial systems, (iii) determination of the atomic structures of membrane receptors, multiprotein complexes and nanoparticles using high resolution electron microscopy, and (iv) determination of the 3D structure, mechanisms of neutralization and cellular entry of HIVThe nature of our work requires expertise in areas spanning from cell and molecular biology to computational biology, physics and engineering. The research background of members in our team reflects this interdisciplinary mix, and we also benefit greatly from collaborations with a variety of scientists both inside and outside NIH.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010278-08
Application #
7291819
Study Section
(LCB)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Fenton, Andrew K; Hobley, Laura; Butan, Carmen et al. (2010) A coiled-coil-repeat protein 'Ccrp' in Bdellovibrio bacteriovorus prevents cellular indentation, but is not essential for vibroid cell morphology. FEMS Microbiol Lett 313:89-95
Milne, Jacqueline L S; Subramaniam, Sriram (2009) Cryo-electron tomography of bacteria: progress, challenges and future prospects. Nat Rev Microbiol 7:666-75
Lengyel, Jeffrey S; Milne, Jacqueline L S; Subramaniam, Sriram (2008) Electron tomography in nanoparticle imaging and analysis. Nanomedicine (Lond) 3:125-31
Bartesaghi, A; Sprechmann, P; Liu, J et al. (2008) Classification and 3D averaging with missing wedge correction in biological electron tomography. J Struct Biol 162:436-50
Narasimha, Rajesh; Aganj, Iman; Bennett, Adam E et al. (2008) Evaluation of denoising algorithms for biological electron tomography. J Struct Biol 164:7-17
Lefman, Jonathan; Morrison, Robert; Subramaniam, Sriram (2007) Automated 100-position specimen loader and image acquisition system for transmission electron microscopy. J Struct Biol 158:318-26
Subramaniam, Sriram; Bartesaghi, Alberto; Liu, Jun et al. (2007) Electron tomography of viruses. Curr Opin Struct Biol 17:596-602
Heymann, Jurgen A W; Hayles, Mike; Gestmann, Ingo et al. (2006) Site-specific 3D imaging of cells and tissues with a dual beam microscope. J Struct Biol 155:63-73
Subramaniam, Sriram (2006) The SIV surface spike imaged by electron tomography: one leg or three? PLoS Pathog 2:e91
Milne, Jacqueline L S; Wu, Xiongwu; Borgnia, Mario J et al. (2006) Molecular structure of a 9-MDa icosahedral pyruvate dehydrogenase subcomplex containing the E2 and E3 enzymes using cryoelectron microscopy. J Biol Chem 281:4364-70

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