Wilson, Richard John (2011) Simulating the kinesin walk : towards a definitive theory. PhD thesis, University of Warwick.

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Abstract

Dementia is a set of incurable, fatal diseases characterised by irreversible
degeneration of the brain. One theory of its cause is the failure of intracellular
transport in the axons of the neurons that compose the brain. Kinesin is a key
motor transporting vital cargo along the axon. We know that this motor is a
bipedal engine stepping forward along a polypeptide track but it is too small
and fast for this motion to be observed using current experimental
techniques. The stepping detail is therefore open to debate. This study firstly
addresses the question of how kinesin steps and secondly pilots a possible
method for investigating transport disruption in silico.
To investigate the detail of stepping, a program has been designed and built
to simulate kinesin traversing its track along a section of axon. The motor is
modelled as simple, interacting agents obeying rules abstracted from known
chemical and binding properties of its components. The agent-based method
has proven useful and efficient on the small scale and has potential for
simulating the larger and more complex system of axonal transport. This
would enable investigation of transport failure in the context of finding a cure
for dementia.
A new model of kinesin stepping has been formulated as a consequence of
performing virtual experiments using the simulation. Analysis of in vivo and in
vitro experimental studies shows that the model accounts for a wide range of
published results, explaining many findings. New experiments are suggested
to test the model based on its falsifiable predictions. The principal conclusion
of this study is that kinesin stepping is rectified Brownian motion.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Library of Congress Subject Headings (LCSH):	Dementia -- Etiology, Kinesin -- Computer simulation
Official Date:	October 2011
Dates:	Date Event October 2011 Submitted
Institution:	University of Warwick
Theses Department:	Molecular Organisation and Assembly in Cells
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Feng, Jianfeng
Sponsors:	Engineering and Physical Sciences Research Council (EPSRC)
Extent:	xvi, 154, [28] p. : ill., charts
Language:	eng
URI:	http://wrap.warwick.ac.uk/id/eprint/49216

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