| NSF Org: |
IOS Division Of Integrative Organismal Systems |
| Recipient: |
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| Initial Amendment Date: | July 18, 2012 |
| Latest Amendment Date: | July 18, 2012 |
| Award Number: | 1145949 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Sridhar Raghavachari
sraghava@nsf.gov (703)292-4845 IOS Division Of Integrative Organismal Systems BIO Directorate for Biological Sciences |
| Start Date: | August 1, 2012 |
| End Date: | July 31, 2016 (Estimated) |
| Total Intended Award Amount: | $310,000.00 |
| Total Awarded Amount to Date: | $310,000.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
5717 CORBETT HALL ORONO ME US 04469-5717 (207)581-1484 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
ME US 04469-5764 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): |
Organization, EPSCoR Co-Funding |
| Primary Program Source: |
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| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.074 |
ABSTRACT
During early development of the central nervous system, the global landscape and concentration of chemical species within the spinal cord serve to direct neuron differentiation and development. The chemical constituency and concentrations of myriad chemical stimulants within the spinal cord signals both the type of neural cells that will develop as well as provide a "trail of breadcrumbs" to direct the precise synaptic connections to other neurons. This research presents a microsystem that generates specific concentration profiles of multiply relevant chemical species to study the development and differentiation of neurons. Using micro and nanofabrication, a microsystem will be designed, fabricated, characterized, and used to generate chemical profiles of known chemicals that affect spinal cord development. An anthology of four mouse spinal cord chemical mediators will be studied: sonic hedgehog (Shh), bone morphogenic protein (BMP), retinoic acid (RA), and noggin, and the spatial and temporal histological distributions of resulting neural cells will be mapped to the imposed chemical mediator concentrations. The advantage of this approach is that cells can be studied in biologically relevant environments without the introduction of the myriad unknown and uncontrolled parameters found in vivo.
This project will support the education and laboratory research training of both graduate and undergraduate students at the University of Maine in a collaborative, multi-disciplinary research project involving biological, micro/nano fabrication, and engineering methods in instrumentation and techniques. The project will also be highlighted in UMaine's "Consider Engineering" summer program for high school students and in several undergraduate and graduate level courses to introduce science & engineering initiates to interdisciplinary research. The microsystem will be extended within these programs/courses to encompass applications involving: cognition models, artificial intelligence, biocomputing, and neural networks.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
This project has successfully demonstrated the application of a microfluidic device to mimic the embryonic biochemical environment and recapitulate the spatial patterning of motor neuron differentiation in vitro. Chemical landscapes of stable and controlled concentration gradients of multiple chemical species (morphogens, mediators, metabolites, etc) were generated within a 3D stem cell culture, in order to faithfully reproduce the biological environment found in the developing nervous systems. We have applied this system to expose pluripotent mouse embryonic stem (ES) cells to overlapping chemical concentration profiles of three well-known morphogens for motor neuron differentiation: Bone Morphogenic Protein (BMP), Retinoic Acid (RA) and Purmorphomine (a Sonic Hedgehog (Shh) signaling antagonist). After 3-5 days, Medial Motor Column (MMC) motor neurons were produced in a spatially defined pattern within the cell culture chamber reminiscent of a dorsal-ventrical slice of the primitive neural tube.
The results of this research have successfully demonstrated a new methodology for the study and experimentation of pluripotent cell differentiation and development in vitro. Results from this work were published in the journal Development (Demers, 2016) and at two international conferences with student authors. Three PhD and three undergraduate students participated in this research project, obtaining hands-on training and experience in the design, microfabrication, assembly and testing of microfluidic devices for gradient generation. Student participants also received training and experience in stem cell culture and differentiation, computer simulations and microscopic imaging, providing them with highly inter and multi -disciplinary skills that are critically needed for transformative research and development.
Last Modified: 10/28/2016
Modified by: Rosemary L Smith
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