William O. Hancock
229 Hallowell Bldg.
Tel: 814-863-0492
Fax: 814-863-0490
Email: wohbio@engr.psu.edu
The intracellular environment is an extremely dynamic place 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 our work 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 to analyze the biochemical and mechanical function of these mutant motors.
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.
Hancock, W.O. and J. Howard. (1999) Kinesin's processivity results from mechanical and chemical coordination
between the ATP hydrolysis cycles of the two motor domains. Proc. Natl. Acad. Sci., 96: 13147-13152.
Hancock, W.0. and J. Howard. (1998) Processivity of the motor protein kinesin requires two heads. Journal of Cell
Biology, 140: 1395-1405.
Coy, D.L., W.O. Hancock, M. Wagenbach and J. Howard. (1999) Kinesin's tail domain is an inhibitory regulator of
the motor domain. Nature Cell Biology, 1: 288-292.
Hancock, W.0., L.L. Huntsman, and A.M. Gordon. (1997) Models of calcium activation account for differences between
skeletal and cardiac force redevelopment kinetics. Journal of Muscle Research and Cell Motility, 18: 671-681.
Hancock, W.0., D.A. Martyn, L.L. Huntsman, and A.M. Gordon. (1996) Influence of Ca2+ on force redevelopment kinetics
in skinned rat myocardium. Biophysical Journal, 70: 2819-2829.