Development of new methods in membrane protein science : tools in aquaporin-based research

Aquaporins are a family of small, integral membrane proteins which facilitate water transport across the plasma membrane of cells in response to osmotic gradients. Since the discovery of these water channels more than 20 years ago, there has been an encouraging advancement in the understanding of th...

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Bibliographic Details
Main Author: To, Janet Yiu Ying
Other Authors: Jaume Torres
Format: Theses and Dissertations
Language:English
Published: 2016
Subjects:
Online Access:http://hdl.handle.net/10356/68722
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Institution: Nanyang Technological University
Language: English
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Summary:Aquaporins are a family of small, integral membrane proteins which facilitate water transport across the plasma membrane of cells in response to osmotic gradients. Since the discovery of these water channels more than 20 years ago, there has been an encouraging advancement in the understanding of their structural and functional roles in human physiology, in particular in water balance disorders, and in cell migration and angiogenesis. However, the progress in aquaporin-based drug discovery is challenged by lack of suitable assays for the identification of modulators, as well as the overall poor druggability of aquaporins. In this work, we have developed a novel high throughput functionality assay which has the potential for biotechnological applications such as drug screening as well as the identification of aquaporin functional mutants. Several biophysical techniques have been employed to assess the binding and inhibitory efficiency of the hits to the human aquaporin 1. Overall, we hope that this research effort can play a part for future treatment of the devastating human diseases related to aquaporins.