| NSF Org: |
MCB Division of Molecular and Cellular Biosciences |
| Recipient: |
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| Initial Amendment Date: | June 19, 2009 |
| Latest Amendment Date: | March 19, 2014 |
| Award Number: | 0844801 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Gregory W. Warr
MCB Division of Molecular and Cellular Biosciences BIO Directorate for Biological Sciences |
| Start Date: | June 15, 2009 |
| End Date: | September 30, 2015 (Estimated) |
| Total Intended Award Amount: | $893,105.00 |
| Total Awarded Amount to Date: | $893,105.00 |
| Funds Obligated to Date: |
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| ARRA Amount: | $893,105.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
10900 EUCLID AVE CLEVELAND OH US 44106-4901 (216)368-4510 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
10900 EUCLID AVE CLEVELAND OH US 44106-4901 |
| 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 Dynamics and Function, UNIMOLECULAR PROCESSES |
| 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
This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Scientific Impacts:
This CAREER project aims to understand the complex feedback network between bile acids and their cellular sensor, the farnesoid X receptor (FXR). Bile acids are ubiquitous physiologic small molecules present in all mammals and most vertebrates that play a central role in digestion. Interestingly, when looking across species, the chemical composition of the bile acid pool is quite diverse. Even within a species, there can be significant variability, as seen in humans. The goals of this project are twofold. First, an approach will be developed using nuclear magnetic resonance (NMR) spectroscopy in conjunction with synthetic organic chemistry to develop bile acid probes to understand how these molecules interact with and signal through FXR. Second, these probes will be used to study central questions of bile acid selectivity between FXR and a class of lipid binding proteins that also bind bile acids. As the goals of this research are twofold, so is the global impact. First, this research project will develop NMR as a tool for dissecting complex binding interactions, which will have the effect of expanding the repertoire of tools that can be used by scientists to study such systems. Further, this work will help to illuminate broader questions about the function of FXR and lipid binding proteins as they relate to bile acid homeostasis.
Broader Impacts:
The pedagogical goals of this project integrate with the research, but focus on biological and chemical education at a more basic and fundamental level. The audience of the described efforts spans from sophomores in high school to sophomores in college and aim to integrate fundamental aspects of both organic chemistry and biochemistry into basic courses at an introductory level. The PI also plans to partner with local high school teachers and integrate their students into scholarly research activities. In addition, a plan is detailed to work with colleagues who are engaged in writing textbooks for introductory classes and local colleagues at Case Western Reserve University to make vertical progress in the way that basic science courses are taught.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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