Hendricks, Adam G. - McGill University - Department of Bioengineering

研究领域

Many essential cellular functions – cell division, motility, protein synthesis, intracellular transport, and others – are driven by motor proteins, a specialized set of enzymes that convert chemical energy into mechanical work. Two motor proteins, kinesin and cytoplasmic dynein, are responsible for the long-range transport of mRNA, proteins, organelles, and signaling molecules along the microtubule cytoskeleton. Active transport by kinesin and dynein is critical for the maintenance of biosynthetic, signaling, and degradative pathways in the cell. Long and highly-polarized cells like neurons are particularly sensitive, and accordingly mutations in kinesin or dynein cause neurodegenerative disease in mouse models and humans. Further, defects in intracellular transport have been linked to many neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer’s disease, and Huntington’s disease. In the complex cellular environment, kinesin and dynein are regulated by interactions with the cytoskeleton, other motor proteins, and binding partners. These interactions allow motors to perform complicated functions such as cell division and the targeted trafficking of intracellular cargoes. The Hendricks lab is focused on understanding how motor proteins function collectively, and how interactions among motor proteins and with the complex cellular environment modulate their behavior. We employ in vitro experiments that incorporate aspects of the cellular environment, high-resolution tracking and manipulation in living cells, and mathematical modeling to understand motor protein dynamics in the cell. In particular, we aim to develop methods to extend the application of single molecule techniques such as optical trapping, FRET, and subpixel resolution tracking to examine motor function in living cells.

近期论文

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Force measurements in living cells reveal collective dynamics of microtubule motors. Hendricks AG, Holzbaur ELF, Goldman YE. Proceedings of the National Academy of Sciences. 2012. 109: 18447-18452. Dynein tethers and stabilizes dynamic microtubule plus-ends. Hendricks AG*, Lazarus JE*, Perlson E, Gardner MK, Odde DJ, Goldman YE, Holzbaur ELF. Current Biology. 2012. 22: 632-637. Motor coordination via tug-of-war mechanism drives bidirectional vesicle transport. Hendricks AG*, Perlson E*, Ross JL*, Schroeder HW III, Tokito M, Holzbaur ELF. Current Biology. 2010. 20: 697-702.