DEVELOPING HIGH THROUGHPUT ORGANOID-BASED PLATFORMS TO STUDY ENTERIC PHYSIOLOGY IN VITRO Public Deposited

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  • March 20, 2019
Creator
  • Williamson, Ian
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
Abstract
  • The human gastrointestinal lumen is a complex environment where microbial resents (microbiota) interact symbiotically and pathogenically with the host intestinal mucosa. Intestinal health is regulated by these interactions as they relate to host genetics and food consumption. Human genetic diversity has long been recognized as a key factor in intestinal health and disease. Recently, appreciation has grown for the importance of microbiota interactions with the host mucosa in maintaining homeostasis and disease. The lack of quantitative in vitro models to investigate interactions in the intestinal mucosa is considered a substantial barrier to investigate intestinal physiology. Organoids represent an attractive model system because they are derived from primary tissues and embody key properties of the native mucosa; however, assaying organoids specifically in high throughput is technically challenging. Organoids grow as spherical monolayers imbedded in hydrogel limiting access to the enclosed ‘lumen’ compartment and complicating longitudinal tracking. Furthermore, the homogeneous composition of the three-dimensional culture environment and the heterogeneity of organoid grown patterns complicates readouts based on organoid grown, size, and morphology. Here, I report on the development and validation of several technologies to address the sampling limitations of organoid systems, facilitating high throughput assays describing mucosa physiology, renewal, and interactions with the microbiota.
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Rights statement
  • In Copyright
Advisor
  • Carroll, Ian
  • MacDonald, Jeffrey
  • Bultman, Scott
  • Allbritton, Nancy
  • Magness, Scott
  • Gomez, Shawn
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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