Ph.D. Bioengineering, University
of Washington, Seattle, 1994
Associate Professor of Bioengineering
229 Hallowell Bldg.
Tel: 814-863-0492
Fax: 814-863-0490
Email: wohbio@engr.psu.edu
Laboratory Website:
Molecular Biomechanics
The intracellular environment is very dynamic, with organelles
and vesicles moving to and fro and material being transported to
various regions of the cell. The molecules responsible for this
movement are motor proteins, which use chemical energy to move
along cytoskeletal tracks. The focus of my lab is to understand
the detailed workings of motor proteins and their role in intracellular
transport and cell motility.
We are concentrating on the kinesin superfamily of microtubule-based
motors, which are involved in broad array of cellular processes
including axonal transport, the positioning of intracellular
organelles, and the movement of chromosomes during cell division.
Kinesins
share a ~340 amino acid motor domain (the head), and members
of the family utilize the motor domain in various ways - to
move towards
the plus- or minus-ends of microtubules (towards the cell periphery
or center, respectively), or even to depolymerize microtubules.
Kinesins are especially interesting because they lie at the interface
of biochemistry and mechanics at the level of a single protein
molecule. To study these motors we are using the tools of modern
molecular biology to isolate and express specific portions
of the motors, and then using a two-pronged attack of enzyme
kinetic
and
motility measurements along with computational modeling to
analyze the biochemical and mechanical function of these mutant
motors.
We are especially interested in Kinesin-2 motors (also called
KIF3A/B), which are involved in intraflagellar transport among
other tasks.
These motors are distinctive because they contain two different
motor domains instead of the usual homodimeric configuration.
Specifically, we are studying how the two heads coordinate
their activities for
processive motility along microtubules.
In addition to these fundamental experiments, we are working
to integrate kinesin motors and microtubules into microfabricated
devices and interface these proteins with nanoparticles and
novel materials. Much of this interdisciplinary work, which
is in collaboration
with colleagues in Chemistry, Electrical Engineering and other
departments, is supported by the PSU Center for Nanoscale Science.
One goal is to develop microfluidic devices for analyte detection
and molecular sorting that use kinesin-driven transport instead
of pressure-driven flow. A second goal is to develop microscale
and nanoscale tools to investigate the role of kinesins and
microtubules in fundamental cellular process such as cell division.
The eventual goal of this work is to better understand the
role of kinesin motors in normal and diseased states, to
define targets
for future therapeutics, and to establish a building blocks
for future nano-scale diagnostic or therapeutic devices.
Representative Publications
Platt, M., G. Muthukrishnan, W.O.
Hancock, and M.E. Williams. 2005. Millimeter scale alignment of magnetic nanoparticle functionalized
microtubules in magnetic fields. Journal of the American Chemical
Society, 127(45):15686-15687.
Huang, Y.M.,
M. Uppalapati, W.O. Hancock, and T.N. Jackson. 2005. Microfabricated capped channels for biomolecular motor-based transport.
IEEE Transactions on Advanced Packaging, 28(4):564-570.
Zhang, Y. and W.O.
Hancock. 2004. The two motor domains of KIF3A/B
coordinate for processive motility and move at different speeds.
Biophysical Journal 87:1795-1804.
Jia, L., S.G. Moorjani, T.N. Jackson
and W.O. Hancock. 2004. Toward
a molecular motor based electronics system for bio-transport and
detection. Biomedical Microdevices 6(1):67-74.
Moorjani, S.G., L. Jia,
T.N. Jackson and W.O. Hancock. 2003. Lithographically
patterned channels spatially segregate kinesin motor activity and
effectively guide microtubule movements. NanoLetters 3:633-637.
Hancock, W.O. and J. Howard. 2002. Kinesins: Processivity and
Chemomechanical Coupling in Motor Proteins, Ed. M. Schliwa, Wiley-VCH,
Weinheim, Germany. 10:243-269.
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