| NSF Org: |
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems |
| Recipient: |
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| Initial Amendment Date: | September 11, 2015 |
| Latest Amendment Date: | September 11, 2015 |
| Award Number: | 1510920 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Stephanie George
CBET Division of Chemical, Bioengineering, Environmental, and Transport Systems ENG Directorate for Engineering |
| Start Date: | September 15, 2015 |
| End Date: | August 31, 2020 (Estimated) |
| Total Intended Award Amount: | $349,999.00 |
| Total Awarded Amount to Date: | $349,999.00 |
| Funds Obligated to Date: |
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| History of Investigator: |
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| Recipient Sponsored Research Office: |
300 TURNER ST NW BLACKSBURG VA US 24060-3359 (540)231-5281 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
333 Kelly Hall Blacksburg VA US 24061-0001 |
| 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): | Engineering of Biomed Systems |
| 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): | 47.041 |
ABSTRACT
PI: Rajagopalan, Padmavathy
Proposal Number: 1510920
The gastrointestinal (GI) tract and the liver are organs in the body that absorb and metabolize a portion of ingested chemicals and nutrients. As such, they serve as defense mechanisms against harmful chemicals and pathogens. This project focuses on engineering an integrated GI and liver tissue to obtain information on how these organs work in unison to metabolize chemicals.
The metabolism of a wide range of chemicals, drugs, and pharmaceuticals is mediated by the dual and complementary actions of the gastrointestinal (GI) tract and liver. However, there is a significant lack in understanding how integrating tissue mimics of these organs function cohesively. Current studies that use simplistic monolayers fail to capture the complex interactions in vivo. The PI proposes integrating three-dimensional (3D) tissue mimics of the liver and GI to obtain physiologically relevant information on their relative contributions to the biotransformation of chemicals. The changes in the function and properties of each tissue upon exposure to chemicals will be investigated under static and dynamic flow conditions. The following research objectives are proposed. 1. Design an integrated GI-Liver platform using a primary intestinal cell sheet and a 3D multi-cellular hepatic organotypic culture model. 2. Investigate the integrated GI-Liver platform in the presence of dynamic flow. 3. Investigate the effect of chemicals using the GI-liver platform. With regard to broader impacts, the PI will conduct K-12 educational outreach through a weeklong activity for female high school students. The students will learn to identify changes in liver and GI systems upon adding chemicals. This activity will enable students to learn how to identify and formulate a research problem, to conduct statistical analyses, and to work in teams.
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.
Intellectual Merit:
The metabolism of drugs and chemicals occurs due to close interactions between the gastrointedstinal tract and the liver. These organs are connected via the portal vein, which carries metabolites and drugs from the intestine to the liver; and the bile duct, which brings the drugs, toxins and bile processed in the liver to the intestine. This enterohepatic circulation affects several physiological functions such as absorption and bioavailability of drugs, bile acid homeostasis and the urea cycle. Together, the gut-liver axis also affects the brain in crucial ways. Understanding how these two organs communicate and work together could reveal new insights into their joint functions. We have cultured rat jejunum explants in vitro and integrated them with hepatocyte cultures. We have also investigated the changes in jejunum function at different locations. Such in vitro models may also be used for testing the effects of other chemicals or drugs in the future.
Broader Impact:
The gut-liver axis plays a critical role in modulating several metabolic and biotransformation processes. Obtaining a fundamental understanding on how these organs communicate provides new information that can be used to understand effects at the molecular, cellular and organ levels. Integration of these tissues could also lead to the identification and acceleration of new insights into these organs and aid in toxicology as well as in the delivery of drugs.
Last Modified: 11/29/2020
Modified by: Padmavathy Rajagopalan
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