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| Antonina Roll-Mecak, Ph.D., Investigator |
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Dr. Roll-Mecak received her undergraduate degree in chemical engineering from The Cooper Union for the Advancement of Science and Art in 1996. She pursued her graduate training in Stephen Burley's laboratory and received her Ph.D. in molecular biophysics from the Rockefeller University in 2002. Her structural and biochemical studies on translation GTPases helped elucidate the assembly mechanism of a functional ribosome in all organisms. She conducted her postdoctoral training with Ron Vale at the University of California, San Francisco where she investigated the mechanism of macromolecular machines that regulate microtubule dynamics. Dr. Roll-Mecak joined NINDS as an investigator in 2009. Dr. Roll-Mecak has received a Burroughs Wellcome Career Award in Biomedical Sciences, a L'Oreal for Women in Science Fellowship Award, a Pathway to Independence Award, a Damon Runyon Cancer Research Postdoctoral Fellowship, and was awarded the Henry W. Reddick Fund Prize and Medal for Mathematics. Her lab combines biophysical and cell biological approaches to understand the mechanism underlying intracellular organization and movement, with a focus on the microtubule cytoskeleton.
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Research Interests:
The overarching scientific question we are interested in is: how do biophysical properties of microtubules and their modifiers produce cell morphology and organismal physiology?
Microtubules are essential polymers rigid enough to serve as the cell's structural scaffold-as rigid, in fact as Plexiglas-but dynamic enough to produce the changes in shape we see during cell division, migration and tissue growth. How do they achieve this dual nature? How do they deliver organelles and other cell components to precise locations at the farthest reaches of the cell, and then reorient to deliver those components to new locales to accommodate the changing requirements of cell physiology? In no other cell type is this requirement more onerous than in the neuron where a large microtubule mass needs to be generated during axonal growth and cargo needs to be transported over distances several thousands of times the diameter of the cell body. Not surprisingly, many neurodegenerative disorders are due to mutations in microtubule dynamics regulators.
We can think of the complex behavior of the microtubule network as a function of several "unit operations",
i.e. the individual actions of cytoskeletal regulators: nucleation, growth and shrinkage, severing and motor movement.
Our goal is to understand the biophysical parameters of these unit operations that are the kernel of cytoskeleton structure and function,
as well as their perturbations in disease states. We take a multifaceted experimental approach, linking atomic resolution information on
cytoskeletal regulators with single molecule dynamics in vitro and the larger context of the cell. We combine X-ray crystallography,
small angle X-ray scattering (SAXS) and electron microscopy (EM) to obtain an atomic resolution snapshot of these tiny protein machines.
Classical kinetics and high-resolution fluorescence microscopy are employed to understand their dynamic behavior and the knowledge of
their fundamental properties garnered from these in vitro studies is used at the cellular level. We welcome biologists, chemists,
physicists and engineers interested in joining our interdisciplinary studies of these fascinating biological polymers.
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Selected Recent Publications:
Roll-Mecak, A. and Vale, R.D. (2008) Structural basis for microtubule severing by the hereditary spastic paraplegia protein spastin., Nature 451(7176), 363-7.
Roll-Mecak, A. and Vale, R.D. (2006) Making more microtubules by severing: a common theme of noncentrosomal microtubule arrays? , J. Cell. Biol. 175 (6), 849-851.
Roll-Mecak, A. and Vale, R. D. (2005) The Drosophila Homologue of the Hereditary Spastic Paraplegia Protein, Spastin, Severs and Disassembles Microtubules., Curr. Biol. 5(7), 650-55.
Roll-Mecak, A., Shin, B-S, Dever, T.E., and Burley, S.K. (2001) Engaging the ribosome: Universal IFs of translation., Trends Biochem. Sci. 26(12), 705-709.
Contact Information:
Dr. Antonina Roll-Mecak
Porter Neuroscience Research Center
Building 35
35 Convent Drive, MSC 3701
Bethesda, MD 20892-3701
Telephone: (415) 476-6381 (office),
(415) 476-6381 (laboratory),
(415) 476-5233 (fax)
Email: Antonina@mail.nih.gov
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