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    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2016 Dissertations (MU)
    • 2016 MU dissertations - Access restricted to UM
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    New gating states of Cystic Fibrosis transmembrane conductance regulator discovered via studying pathogenic mutations, pharmacological reagents and ATP analogs.

    Lin, Wen-Ying
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    [PDF] research.pdf (4.192Mb)
    [PDF] short.pdf (85.69Kb)
    Date
    2016
    Format
    Thesis
    Metadata
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    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Cystic Fibrosis (CF), caused by the loss of function in the gene for the protein cystic fibrosis transmembrane conductance (CFTR), is one of the most common lethal genetic diseases in the United States. By studying the structural/functional properties of CFTR, we are able to understand the molecular nature of this protein as well as to provide the potential target for drug designs. In my PhD study, I applied patch-clamp technique to explore the gating function of CFTR. Specifically, in my thesis, we approached a more complete CFTR gating scheme through three different ways. First, we proposed two new states need to be added to the original gating scheme to address unexpected results observed in G551D-CFTR, the third most common disease-associated mutant. Second, by studying the gating mechanism of NPPB on CFTR, we further confirmed the existence of these two states. Third, an ATP analog, 2-deoxy-ATP was used to explore the gating pathway provided by these two new states. This study not only bears the significance of the fundamental function of a single molecule, but also provides a new direction in the future drug development.
    URI
    https://hdl.handle.net/10355/57409
    https://doi.org/10.32469/10355/57409
    Degree
    Ph. D.
    Thesis Department
    Pharmacology (MU)
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    Access is limited to the campuses of the University of Missouri.
    Collections
    • 2016 MU dissertations - Access restricted to UM
    • Medical Pharmacology and Physiology electronic theses and dissertations (MU)

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