Schultz Laboratory, 319
Molecular Architecture and Function of the Microtubule Cytoskeleton
We are interested in understanding how cells acquire their shape, position organelles, move materials, and segregate chromosomes during cell division. These features are essential for life and organized by the microtubule cytoskeleton, which resembles the skeletal system that supports our human body. Each cell type and shape requires a specific microtubule architecture. For instance, long and bundled microtubules make up the axonal extensions of a nerve cell that can reach up to 1 meter in length, whereas a spherical microtubule network renders a lymphocyte perfectly round. In contrast to the human skeleton, the microtubule cytoskeleton is also highly dynamic. Most cells regularly undergo cell division, during which the cell-type specific interphase microtubule network is completely disassembled and replaced by short and dynamic microtubules of the mitotic spindle to capture, align and then segregate chromosomes.
How is a Specific Microtubule Architecture Established at the Molecular Level?
Microtubules are cylindrical and dynamic polymers that consist of the protein tubulin. The biological function of the microtubule cytoskeleton relies on the precise arrangement of microtubules in the cell. To achieve this organization, microtubule associated proteins generate, sever, polymerize, shrink, bundle, anchor, or move microtubules. We want to understand these functionalities mechanistically and use this insight to explain how they ultimately result in the self-organization of the microtubule cytoskeleton.
We employ two complementary approaches that allow us to both look at structural detail of microtubule effectors and explain their function in the biological context. To study the mechanism by which microtubules are organized at a structural level, we use biophysical methods, electron microscopy and X-ray crystallography. To understand the dynamic assembly of the microtubule cytoskeleton, we combine biochemical and cell biological techniques along with advanced light microscopy methods.
Our goal is to identify and characterize new mechanisms that establish the cellular microtubule architecture. This will ultimately reveal how the microtubule cytoskeleton builds cellular structures to give cells their shape, position organelles, serve as tracks that move materials, generate force for movement, and segregate chromosomes.
Petry, S.; Groen, A. C.; Ishihara, K.; Mitchison, T. J.; Vale, R. D., "Branching Microtubule Nucleation in Xenopus Egg Extracts Mediated by Augmin and TPX2." Cell 2013, 152 (4), 768-777.
Petry, S.; Pugieux, C.; Nedelec, F. J.; Vale, R. D., "Augmin promotes meiotic spindle formation and bipolarity in Xenopus egg extracts." Proceedings of the National Academy of Sciences of the United States of America 2011, 108 (35), 14473-14478.
Petry, S.; Vale, R. D., "A new cap for kinetochore fibre minus ends." Nature Cell Biology 2011, 13 (12), 1389-1391.
Uehara, R.; Nozawa, R.-s.; Tomioka, A.; Petry, S.; Vale, R. D.; Obuse, C.; Goshima, G., "The augmin complex plays a critical role in spindle microtubule generation for mitotic progression and cytokinesis in human cells." Proceedings of the National Academy of Sciences of the United States of America 2009, 106 (17), 6998-7003.
Weixlbaumer, A.; Jin, H.; Neubauer, C.; Voorhees, R. M.; Petry, S.; Kelley, A. C.; Ramakrishnan, V., "Insights into Translational Termination from the Structure of RF2 Bound to the Ribosome." Science 2008, 322 (5903), 953-956.
Petry, S.; Weixibaumer, A.; Ramakrishnan, V., "The termination of translation." Current Opinion in Structural Biology 2008, 18 (1), 70-77.
Weixlbaumer, A.; Petry, S.; Dunham, C. M.; Selmer, M.; Kelley, A. C.; Ramakrishnan, V., "Crystal structure of the ribosome recycling factor bound to the ribosome." Nature Structural & Molecular Biology 2007, 14 (8), 733-737.
Selmer, M.; Dunham, C. M.; Murphy, F. V.; Weixlbaumer, A.; Petry, S.; Kelley, A. C.; Weir, J. R.; Ramakrishnan, V., "Structure of the 70S ribosome complexed with mRNA and tRNA." Science 2006, 313 (5795), 1935-1942.
Petry, S.; Brodersen, D. E.; Murphy, F. V.; Dunham, C. M.; Selmer, M.; Tarry, M. J.; Kelley, A. C.; Ramakrishnan, V., "Crystal structures of the ribosome in complex with release factors RF1 and RF2 bound to a cognate stop codon." Cell 2005, 123 (7), 1255-1266.