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 #
5R01GM064473-04
Application #
6849333
Study Section
Special Emphasis Panel (ZRG1-SSS-U (03))
Program Officer
Deatherage, James F
Project Start
2002-02-01
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
4
Fiscal Year
2005
Total Cost
$308,001
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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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
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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
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

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