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Title: Developing our understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) channel
Author: Hesketh, Sophie Janine
ISNI:       0000 0004 9358 1579
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2020
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Transient receptor potential (TRP) melastatin 2 (TRPM2) is a non-selective cation channel of the TRP channel superfamily. It plays key roles in mediating oxidative stress and immune responses and is endogenously activated at ~37 °C – human body temperature. Here, the styrene-maleic acid (SMA) co-polymer and a combination of detergents were used to biochemically, biophysically and structurally characterise the TRPM2 cation channel in vitro. Through these experiments, fascinating insights were gained into TRPM2 structure and function as a temperature sensor, as well as the role of native lipids in channel stabilisation. The use of SMA was crucial to the success of these studies, but inherent issues with the polymer can render it unsuitable for use with some biophysical techniques – particularly mass spectrometry (MS) and electron microscopy (EM), and functional assays requiring divalent cations. In light of this, an ‘SMA-exchange’ was also developed, whereby the power of SMA as a solubilisation agent is utilised for extraction and purification, then exchanged for another solubilisation platform to enhance compatibility with downstream applications. Overall, novel structural and functional mechanisms of the TRPM2 cation channel have been suggested, and when bottlenecks were met in TRPM2 characterisation, an exchange method was developed to circumvent the issues.
Supervisor: Muench, Stephen ; Sivaprasadarao, Asipu Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available