Download Understanding Transport by Motor Proteins With the Help of Image

Complexity DTC Miniproject
Markus Kirkilionis
[email protected]
Understanding Transport by Motor Proteins With the Help
of Image Analysis Tools
Research objectives
Motor proteins are molecular machines that convert chemical energy from
ATP hydrolysis into mechanical work (motor transport, or short MT), which
powers cell motility. Over the last ten years, image analysis, singlemolecule techniques and structural studies have led to rapid progress in
understanding how these biological motors operate. How do they move?
How do they generate force? How much fuel do they consume, and with
what efficiency?
We like to understand how different types of motor proteins in
combination with their ‘tracks’, actin filaments that form parts of the
cytoskeleton, create one of the major transport systems of the cell on
which all higher forms of life depend. We consider a typical so-called
multi-scale analysis forming part of image analysis: How do the molecular
properties affect the random walk a typical cargo in the cell performs? We
will study this problem by evaluating different digital video sequences.
Why is it interesting?
Image analysis has become a major tool of scientific discovery across all
physical scales, from satellite images to electron microscopy. Whereas of
course a single image is something static it has become clear that we
need to study processes as well, which are typically associated with image
sequences. Transport is such a typical dynamic process we need to
understand. During evolution cells have developed a sophisticated such
transport mechanism, based on molecular motors that require energy
input. This is in contrast to transport by pure diffusion where no additional
input other than thermal fluctuations are required. The problem to
understand why this more directed transport in the cell is needed would
solve a major evolutionary riddle and help to potentially combat some
cellular transport linked diseases.
Techniques required.
The main techniques are
(i) image analysis of digitally recorded microscopy images.
Detecting forces and motion.
(ii) Mathematical modeling of the cellular transport process as
part of the image analysis. This might be shifted to a
later stage as (i) might already be sufficient for a miniproject.
The images show the image analysis process and a a typical video
sequence capturing a motor protein in action. (Courtesy of R. Cross,
Warwick).
Prospective deliverables.
- Defining an image analysis protocol of MT (this project).
- Building a first model for the MT motility assay, with motor density,
microtubule length and motor mechanical, chemical & mechano-chemical
rate constants as variables. This would then have predictive power: for
example for a non-processive motor there should be a minimum density
of motors to produce continuous motility, a microtubule length cut-off,
and so on.
Who should benefit from this research?
- All sciences where image analysis is relevant.
-
Life sciences especially, cell biology and medicine
Complex systems research in its unique combination of data
intensive analysis and modeling of a highly complex system.
Identification of unified principles of transport.
Outline of avenues for a follow-up PhD project.
The path to a PhD for this problem is quite clear. After having established
an image analysis protocol of transport efficiency under various conditions
we like to establish a predictive model of motor transport taking motor
protein densities into account. This will be part of an extended image
analysis.
References:
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The kinetic mechanism of kinesin, by Robert A. Cross. Trends in
Biochemical Sciences, Volume 29, Issue 6, 1 June 2004, Pages 301-309.
Mechanics of Motor Proteins and the Cytoskeleton, a book by
Jonathon Howard, Max Planck Institute for Molecular Cell Biology and
Genetics.
Geometric quantification of the plant endoplasmic reticulum. By
Bouchekhima AN, Frigerio L, Kirkilionis M. J Microsc. 2009
May;234(2):158-72. [MEDLINE] DOI: 10.1111/j.13652818.2009.03158.x