| NSF Org: |
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems |
| Recipient: |
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| Initial Amendment Date: | July 13, 2017 |
| Latest Amendment Date: | July 13, 2017 |
| Award Number: | 1741588 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Steven Peretti
speretti@nsf.gov (703)292-4201 CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering |
| Start Date: | January 1, 2017 |
| End Date: | December 31, 2017 (Estimated) |
| Total Intended Award Amount: | $25,988.00 |
| Total Awarded Amount to Date: | $81,513.00 |
| Funds Obligated to Date: |
FY 2012 = $41,000.00 FY 2013 = $14,525.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
110 21ST AVE S NASHVILLE TN US 37203-2416 (615)322-2631 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
Biomedical Engineering PMB 351631 Nashville TN US 37235-0002 |
| 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): | Cellular & Biochem Engineering |
| Primary Program Source: |
01001213DB NSF RESEARCH & RELATED ACTIVIT 01001314DB NSF RESEARCH & RELATED ACTIVIT |
| 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): | 47.041 |
ABSTRACT
The overall goal of this proposal is to develop an integrated research and educational plan focused on cellular migration. This award, supported by the CBET division of the National Science Foundation, will enable the development of novel tools to uncover the mechanisms governing endothelial cell chemotaxis. Research and education will be integrated through their common focus on cell-extracellular matrix interactions. The research goal of this proposal is to use an approach inspired by directed evolution to study chemotaxis. The natural cell-to-cell variations and heterogeneities within a population will be exploited to uncover basic mechanisms that drive efficient chemotaxis in endothelial cells in response to vascular endothelial growth factor (VEGF). A novel chemotactic device will be developed which sorts endothelial cells based on the robustness of their response to chemotactic gradients of VEGF. These sub-populations will be analyzed for underlying molecular differences that are contributing to the differential chemotactic behaviors. Experiments will be performed in both 2D and 3D microenvironments and compared. This work has the potential to uncover critical insights into the molecular regulation of endothelial cell chemotaxis. Moreover, it has clear implications in the field of tissue engineering, where controlled, directed endothelial cell migration could enable the engineering of vascular networks in tissue engineered scaffolds, and in cancer research, where a better understanding of angiogenesis could enable the development of more targeted therapeutics to prevent endothelial cell chemotactic response. The broader impact of this CAREER program is the development of an interdisciplinary learning environment that connects biology and engineering across multiple length scales (molecular, cellular and tissue level). Innovative teaching methodologies and outreach activities will be employed to introduce middle and high school girls in the local, underserved, rural community to concepts in biology and engineering in a tractable way and to promote lifelong learning in science.
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.
Cell migration is essential to numerous processes: embryonic development, cancer metastasis and wound healing, to name just a few. However, cell migration can be difficult to study because there is inherent heterogeneity in cells and cell behaviors. For instance, it is known that cells have the capacity to move, however even within a clonal population of cells, one can find cells that move slowly and others that move quickly. It has been speculated that it is the cells that exhibit these outlier behaviors of migration are those that can cause defects in development or in the progression of cancer, as examples. In the first objective our proposal, we developed a methodology for sorting out the most migratory cells from the weakest migrators. Our goal was to create more uniform populations of cells so that we could dissect out the molecular drivers of migration. In Objective 2, we analyzed the cells and their distinct molecular profiles. Lastly in Objective 3, we compared cell migration in a variety of environments to find commonalities. We were highly successful and uncovered several novel findings. First, we discovered that migration behavior is hereditary. Mother cells and daughter cells migrate similarly. This points to genetic alterations that contribute to migration behavior. We identified several key molecules mediating these behaviors. Most notably, we found that the migration behavior in petri dishes did not predict migration behavior in vivo. This work lays the foundation to ask whether other cells types follow similar trends. Such data is fundamental to our understanding of cell migration and its role in the body.
Throughout the duration of the grant, we were also heavily involved in outreach. We designed and implemented a yearly 3 day workshop, hosting ~15 high schoolers from rural New York through the 4H program. In the workshop, graduate and undergraduate students taught the participants about bioengineering and the use of tissue engineered models. The high school participant worked in the lab, running their own experiments and testing their own hypotheses.
Last Modified: 03/23/2018
Modified by: Cynthia A Reinhart-King
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