Molecular Motors: From Mechanics to Disease

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Date/Time:Monday, 26 Jan 2015 from 4:10 pm to 5:00 pm
Location:Physics 0003
Phone:515-294-5441
Channel:College of Liberal Arts and Sciences
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George Shubeita The University of Texas at Austin

Abstract: Much like a city, living cells are organized, and maintaining their organization is essential for their proper functioning. To position micrometer-sized vesicles and organelles inside the cell at the right place and in a timely fashion the cell shuttles these cargoes along a network of intracellular roads (microtubules and actin filaments) using a set of molecular motor proteins (kinesin, dynein and myosin). These motor proteins use the energy released by ATP hydrolysis to generate the force they need to haul the cargoes; thus, measuring that force amounts to directly probing their function. Measuring the piconewoton forces that motors exert in their native cellular environment enabled us to count the number of motors hauling individual cargoes, and to test physical models of intracellular transport. Given the ubiquity of molecular motors, failure in regulating their function can result in disease. Neurodegenerative diseases such as Alzheimer's, Huntington and Amyotrophic Lateral Sclerosis, for example, have been linked to motor malfunction. Using a combination of genetic, biochemical and biophysical tools in a fruit fly model of Alzheimer's disease, we established the mechanism by which the motor regulator GSK-3 alters transport when present in the elevated levels found in Alzheimer's patients. Our findings have implications on the development Alzheimer's drugs targeting GSK-3.

Bio: George Shubeita earned his Bachelor's degree in physics from Birzeit University and his PhD in physics from The University of Lausanne, Switzerland. His doctoral work focused on using fluorescence resonance energy transfer (FRET) to enhance optical imaging resolution below the diffraction limit. As a Paul Siegler/Agouron Fellow of the Helen Hay Whitney Foundation at the University of California Irvine, he started studying the function and regulation of molecular motor proteins that shuttle cargoes within living cells. He developed the methodology and performed the first optical trapping measurements of motor forces moving individual cargoes in their native living cell. His work in the physics department at the University of Texas at Austin continues to combine biophysical, genetic and biochemical tools to probe motor regulation in health and disease. He studies how multiple similar and dissimilar molecular motors interact, how their transport properties are governed by the complex and crowded cellular environment and co-factors present in vivo, and how failure in motor regulation relates to disease.