Award Abstract # 1553637
CAREER: Multiscale Modeling of Axonal Cytoskeleton Dynamics and Axonal Transport

NSF Org: DMS
Division Of Mathematical Sciences
Recipient: OHIO STATE UNIVERSITY, THE
Initial Amendment Date: February 25, 2016
Latest Amendment Date: June 2, 2020
Award Number: 1553637
Award Instrument: Continuing Grant
Program Manager: Junping Wang
jwang@nsf.gov
 (703)292-4488
DMS
 Division Of Mathematical Sciences
MPS
 Directorate for Mathematical and Physical Sciences
Start Date: July 1, 2016
End Date: October 31, 2020 (Estimated)
Total Intended Award Amount: $408,628.00
Total Awarded Amount to Date: $408,628.00
Funds Obligated to Date: FY 2016 = $163,753.00
FY 2018 = $53,431.00

FY 2019 = $0.00

FY 2020 = $0.00
History of Investigator:
  • Chuan Xue (Principal Investigator)
    cxue@umn.edu
Recipient Sponsored Research Office: Ohio State University
1960 KENNY RD
COLUMBUS
OH  US  43210-1016
(614)688-8735
Sponsor Congressional District: 03
Primary Place of Performance: Ohio State University
Columbus
OH  US  43210-1016
Primary Place of Performance
Congressional District:
03
Unique Entity Identifier (UEI): DLWBSLWAJWR1
Parent UEI: MN4MDDMN8529
NSF Program(s): Engineering of Biomed Systems,
MATHEMATICAL BIOLOGY,
MSPA-INTERDISCIPLINARY,
Division Co-Funding: CAREER
Primary Program Source: 01001617DB NSF RESEARCH & RELATED ACTIVIT
01001819DB NSF RESEARCH & RELATED ACTIVIT

01001920DB NSF RESEARCH & RELATED ACTIVIT

01002021DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1045, 8007, 8091
Program Element Code(s): 534500, 733400, 745400, 804800
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.049

ABSTRACT

The cell cytoskeleton is a dynamic intracellular polymer system providing highways for the active transport of various proteins and organelles inside a cell. Perturbations of intracellular transport can lead to intracellular traffic jams, cell death, and various diseases, analogous to the damage to a city when the transportation system breaks down. The investigator will develop multiscale models and methods to understand how the cytoskeleton and intracellular transport are affected in diseases inside an axon, which is a long thin projection of a neuron. The research results will have profound implications for understanding neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). It is anticipated that the new mathematical models can be readily generalized to other cellular transport problems. The new mathematical theory on interacting particle systems will have wide applications in biology and social sciences. The research plan will be tightly integrated with the educational plan that will engage graduate students on interdisciplinary research and expose K-12 students to mathematical biology and scientific computing through residential summer camps. This project will also broaden the participation of underrepresented groups in STEM fields.

The axonal cytoskeleton is an intracellular polymer system that is responsible for the active transport of various cargoes along an axon. Disruptions of the axonal cytoskeleton and axonal transport, including radial segregation of the cytoskeleton and abnormal accumulations of cargoes, have been observed in many neurodegenerative diseases, but the underlying mechanisms remain unclear. The investigator will develop multiscale models to study the axonal cytoskeleton dynamics and axonal transport in health and disease. There are three aims. The first is to derive macroscopic models for the organization of the axonal cytoskeleton in cross-section from microscopic models, and use them to investigate the striking radial segregation of the axonal cytoskeleton in disease. The second is to develop new multiscale modes for cargo transport along an axon that incorporate cargo-cargo interactions, and use them to investigate potential mechanisms that cause focal accumulations of cargoes, which are early hallmarks of nerve degeneration. The third is to develop fully three-dimensional stochastic models for the axonal cytoskeleton dynamics and axonal transport for investigation of biological questions that concern dynamics near the nodes of Ranvier, which are naturally occurring narrowing points in large axons. The multiscale modeling strategy and the close collaboration with experimentalists will lead to significant insights into the biological problem and help guide new experiments.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

Note:  When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

Thomas Hillen, Kevin J Painter, Magdalena A Stolarska, and Chuan Xue "Multiscale phenomena and patterns in biological systems: special issue in honour of Hans Othmer" Journal of Mathematical Biology , v.80 , 2020 , p.275
Wenrui Hao and Chuan Xue "Spatial Pattern Formation in Reaction-Diffusion Models: A Computational Approach" J Math Biology , v.80 , 2020 , p.521
X. Lai, A. Brown and C. Xue "A stochastic model that explains axonal organelle pileups induced by a reduction of molecular motors" J Royal Society Interface , 2018 , p.submitted
X. Xue, C. Xue and M. Tang "The role of intracellular signaling in the stripe formation in engineered E. coli populations." PLoS Computational Biology , 2018

Please report errors in award information by writing to: awardsearch@nsf.gov.

Print this page

Back to Top of page