The cilium is a complex motile cell organelle that occurs widely in eukaryotic cells, in protozoa and invertebrate metazoa as well as vertebrates. The structure and mechanism of motility of this organelle are conserved throughout evolution, but details of the molecular basis of motion remains unsolved. The overall aim of this project is to build a functional computer model of the ciliary axoneme at high resolution. This dynamic model would incorporate the structural, mechanical and force-generating properties of each of several critical axonemal components to illustrate how a bend is formed and how a bending wave is propagated along a complete axoneme at a level of resolution unobtainable previously. Appropriate measurements of structural and other features in electron micrographs to define missing elements, such as the properties of the interdoublet links, would be combined with analysis of the physical properties of the system at various levels of complexity, to permit the computation of time-dependent structural changes in the model beginning with doublet sliding. Constraints will then be introduced to generate a model of axonemal splitting and then of bending. The successful completion of the working model with appropriate software packing will be a powerful tool of organelle structural biology to be used by future investigators.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR009785-02
Application #
2285100
Study Section
Special Emphasis Panel (ZRG7-SSS-9 (08))
Project Start
1994-05-01
Project End
1997-04-30
Budget Start
1995-05-17
Budget End
1996-04-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Taylor, H C; Satir, P; Holwill, M E (1999) Assessment of inner dynein arm structure and possible function in ciliary and flagellar axonemes. Cell Motil Cytoskeleton 43:167-77
Holwill, M E; Foster, G F; Hamasaki, T et al. (1995) Biophysical aspects and modelling of ciliary motility. Cell Motil Cytoskeleton 32:114-20
Hamasaki, T; Holwill, M E; Barkalow, K et al. (1995) Mechanochemical aspects of axonemal dynein activity studied by in vitro microtubule translocation. Biophys J 69:2569-79