Rollins, Jay; Whitney, Jordan; Hope, Sandra; Mizrachi, Dario (Brigham Young University)
Faculty Advisor: Mizrachi, Dario (Brigham Young University, Physiology and Developmental Biology)
Epithelial and endothelial tissues form selectively permeable barriers, with the permeability largely controlled by intercellular tight junctions. Claudin (CLDN) proteins are critical components of these tight junctions, making them the gatekeepers that control the paracellular space in multicellular organisms. CLDN proteins are thus targets for studies on epithelial and endothelial absorption, to therefore learn how to regulate them for potential drug delivery or therapeutics. CLDN characterization is still in progress. Previously, the relative strength of each member of the CLDN family was unknown. Additionally, no high-throughput method to study absorption enhancers or inhibitors had been found.
Through CLDN expression in Escherichia coli, we determined the relative strength of each CLDN protein and confirmed the effects of various absorption enhancers from previous studies. Therefore, we propose that CLDN expression in Escherichia coli is a valid model for the study of tight junctions and that, through flow cytometry, it is a high-throughput method for interrogating large libraries of potential drug delivery compounds. Using CLDN 2 because of its role in cancer-metastasis prevention and its measured sensitivity towards epithelial modulators, we studied a fifty thousand compound library (DIVERSet-CL Library) to identify absorption moderators, drug delivery compounds, and possible cancer-metastasis prevention.