A fundamental theme in cell biology centers on the structure-function relationships of the macromolecular complexes responsible for cellular events. One goal of structural biology is to obtain a description of these macromolecular machines in their different functional states and in their structural environment. While it is possible to image large macromolecular assemblies, sub-cellular structures and even cells with the aid of electron microscopy, the resolution restrictions of the resulting maps most often precludes direct high-resolution interpretation of these reconstructions. We propose to develop a molecular pattern recognition system for identification and location of molecules in the context of complex structural environments. We will concentrate our efforts on simplified systems of actin- and microtubule-related assemblies. A tight coupling of the development of the methodology with applications to these biologically highly significant assemblies will be employed . This way we will obtain immediate feedback as to how the system performs in practice while providing valuable insight into those systems. For each step, computer-generated model systems will also be used as a tool for development and evaluation. Documentation, tutorials and an easy to-use interface will be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064473-05
Application #
7010690
Study Section
Special Emphasis Panel (ZRG1-SSS-U (03))
Program Officer
Deatherage, James F
Project Start
2002-02-01
Project End
2008-01-31
Budget Start
2006-02-01
Budget End
2008-01-31
Support Year
5
Fiscal Year
2006
Total Cost
$300,762
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Auer, Manfred; Koster, Abrahram J; Ziese, Ulrike et al. (2008) Three-dimensional architecture of hair-bundle linkages revealed by electron-microscopic tomography. J Assoc Res Otolaryngol 9:215-24
Garduno, Edgar; Wong-Barnum, Mona; Volkmann, Niels et al. (2008) Segmentation of electron tomographic data sets using fuzzy set theory principles. J Struct Biol 162:368-79
van der Heide, Peter; Xu, Xiao-Ping; Marsh, Brad J et al. (2007) Efficient automatic noise reduction of electron tomographic reconstructions based on iterative median filtering. J Struct Biol 158:196-204
Janssen, Mandy E W; Kim, Eldar; Liu, Hongjun et al. (2006) Three-dimensional structure of vinculin bound to actin filaments. Mol Cell 21:271-81
Volkmann, Niels; Liu, HongJun; Hazelwood, Larnele et al. (2005) The structural basis of myosin V processive movement as revealed by electron cryomicroscopy. Mol Cell 19:595-605
Marsh, Brad J; Volkmann, Niels; McIntosh, J Richard et al. (2004) Direct continuities between cisternae at different levels of the Golgi complex in glucose-stimulated mouse islet beta cells. Proc Natl Acad Sci U S A 101:5565-70
Volkmann, Niels (2004) An approach to automated particle picking from electron micrographs based on reduced representation templates. J Struct Biol 145:152-6
Volkmann, Niels; Hanein, Dorit (2003) Electron microscopy. Methods Biochem Anal 44:115-33
Volkmann, Niels; Hanein, Dorit (2003) Docking of atomic models into reconstructions from electron microscopy. Methods Enzymol 374:204-25
Volkmann, Niels; Ouyang, Greta; Trybus, Kathleen M et al. (2003) Myosin isoforms show unique conformations in the actin-bound state. Proc Natl Acad Sci U S A 100:3227-32

Showing the most recent 10 out of 11 publications