COMPUTER MODELING OF CILIARY MECHANISMS

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.