Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
PROJECT SUMMARY Chronic idiopathic constipation is a functional gastrointestinal disorder that affects up to 1 in 5 children. As a pediatric surgeon, often the only effective treatments I can offer are intestinal resection or diversion. Thus, I strive to better understand the mechanisms that result in this cryptic disease. The K08 program has been an ideal foundation to develop the technical and scientific skills I need to make a translational impact for my patients. Through my career development award, I have been able to explore the effect of biomechanical forces on the enteric nervous system (ENS) as a driver of persistent bowel dysfunction in Hirschsprung disease. In the last few years, we have uncovered that the chronically distended, ganglionic intestine in Hirschsprung disease has altered tissue mechanical properties. We have shown that the biomechanical forces of stretch and stiffness impact enteric neuronal phenotype and function and we have tied these changes to the mechanoreceptor, Piezo1. Taken together, our preliminary findings suggest that bowel dysfunction may be driven by mechanically- induced changes in the ENS microenvironment. The concept that biomechanical forces regulate enteric neuronal behavior and intestinal function is applicable to many gastrointestinal diseases. However, it is difficult to discern the contribution of individual biomechanical forces and the response of different cell types to biomechanical force using in vivo models alone. Thus, we seek to leverage this R03 mechanism to develop new methods and new technology to study the effect of biomechanical forces on enteric neurons and glia in vitro. This proposal lays out a two-year plan to optimize a novel engineered three-dimensional (3-D) microfluidic, co-culture system to determine the impact of biomechanical forces on enteric neurons and glia. The current proposal builds on the premise of my K08, that biomechanical forces influence ENS behavior to affect intestinal function, with two aims: (1) to test the role of biomechanical forces (stretch and shear stress) on enteric neuronal morphology, neuroglial differentiation, and neuronal function; (2) to determine how neuroglial interactions shape the ENS response to biomechanical forces. This project will leverage an established organ- on-chip platform, enteric neuronal stem cell culture, in vitro modeling, and cutting-edge cellular and molecular biology techniques to achieve these goals. Completion of these aims will further my transition to independence as an investigator and lead to a new mechanistic understanding of gastrointestinal function with the potential to improve the quality of life for millions of adult and pediatric patients.
Grant Summary
Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $121K for university, nonprofit, healthcare org. Applications are due 2028-04-30 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $121K
2028-04-30
- 1Confirm your organization is eligible for Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system: Frequently Asked Questions
Who is eligible for the Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system?
Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system provide?
Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system provides up to $121K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system deadline?
Applications for Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system are due 2028-04-30 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system?
To apply for Engineering a gut-on-chip model to study biomechanical forces on the enteric nervous system, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.