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Award Abstract #1254893

CAREER: An Integrated Approach to Neuron Mechanics: Deciphering the Functional, Mechanical, and Structural Interactions between Microtubules and Actin

NSF Org: CMMI
Div Of Civil, Mechanical, & Manufact Inn
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Initial Amendment Date: December 18, 2012
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Latest Amendment Date: April 11, 2016
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Award Number: 1254893
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Award Instrument: Standard Grant
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Program Manager: David Fyhrie
CMMI Div Of Civil, Mechanical, & Manufact Inn
ENG Directorate For Engineering
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Start Date: April 1, 2013
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End Date: March 31, 2018 (Estimated)
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Awarded Amount to Date: $410,000.00
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Investigator(s): Megan Valentine valentine@engineering.ucsb.edu (Principal Investigator)
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Sponsor: University of California-Santa Barbara
Office of Research
SANTA BARBARA, CA 93106-2050 (805)893-4188
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NSF Program(s): Biomechanics & Mechanobiology
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Program Reference Code(s): 024E, 027E, 028E, 1045, 116E, 9102, 9178, 9231, 9251, SMET
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Program Element Code(s): 7479

ABSTRACT

The research objective of this Faculty Early Career Development (CAREER) award is to use a suite of custom imaging and microscale manipulation tools to investigate the interdependence of motility, adhesion and transport in neurons. Neurons are specialized cells, with highly elongated geometries, that form mechanically connected networks to enable transmission of signals in the nervous system. The development of healthy neural networks depends on the action of filamentous cytoskeletal structures: actin guides neuron growth and adhesion, while microtubules serve as the tracks for the long-distance intracellular transport of proteins and organelles that is required to maintain the extended cell protrusions. Studies conducted under this award will determine the extent and nature of the coordination between the actin and microtubule structures by measuring how errors in long-distance transport affect cell adhesion and motility, and how chemically- and mechanically-engineered scaffolds that modulate adhesion affect transport. The effects of sudden impact injury on single neuron mechanics, adhesion and transport will also be determined.

If successful, this research will provide a new paradigm for the experimental investigation of neurons (-). One that integrates distinct features such as adhesion or transport into one comprehensive model of neuron function. Ultimately, the results will lead to the design of improved neural devices and implantation materials, and novel treatment strategies for a wide range of neurological disorders and traumatic brain injuries (TBI). The educational goals are to include undergraduate students in all aspects of research, and to develop new teaching material on the emerging field of neuron mechanics. A new internship program, Veteran-student Internships in Biomechanics Research and NeuroTechnology (VIBRANT) will be developed to bring veteran students from local community colleges to campus to pursue independent research. One-on-one mentoring and professional development opportunities will be provided to encourage and empower veteran students to pursue science and engineering degrees.


PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Benjamin J. Lopez, Megan T. Valentine. "Mechanical effects of EB1 on microtubules depend on GTP hydrolysis state and presence of paclitaxel," Cytoskeleton, v.71, 2014.

Christian Vaca, Yali Yang, Megan T. Valentine, Alex J. Levine. "Bond breaking dynamics in semiflexible networks under load," Soft Matter, 2015.

Benjamin J. Lopez, Megan T. Valentine. "Molecular control of stress transmission in the microtubule cytoskeleton," BBA - Molecular Cell Research, 2015.

Benjamin J. Lopez, Megan T. Valentine. "Mechanical effects of EB1 on microtubules depend on GTP hydrolysis state and presence of paclitaxel," Cytoskeleton, v.71, 2014, p. 530.

Nicholas A. Zacchia, Megan T. Valentine. "Design and optimization of arrays of neodymium iron boron-based magnets for magnetic tweezers applications," Review of Scientific Instruments, v.86, 2015, p. 053704. 

Benjamin J. Lopez and Megan T. Valentine. "The TIP Coordinating Protein EB1 is Highly Dynamic and Diffusive on Microtubules, Sensitive to GTP Analog, Ionic Strength, and EB1 Concentration," Cytoskeleton, v.73, 2016, p. 23. 

 

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