Development of Bioluminescent Biosensors Monitoring Activity of the Merlin Tumour Suppressor
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Authors
Pipchuk, Alex
Date
Type
thesis
Language
eng
Keyword
Biosensor , Complementation Assay , Hippo Pathway , LATS , Luciferase , Merlin , NanoBiT , NanoLuc
Alternative Title
Abstract
All solid tumours share the ability to circumvent or overcome contact inhibition of proliferation (CIP), the process by which cell-cell contacts engage signalling to stop proliferation. Merlin, an ERM-like protein, plays a crucial role in CIP and is inactivated in a wide variety of cancers, suggesting that it is a tumour suppressor of general importance in cancer biology. Although the role of Merlin in cancer has been investigated extensively, this protein lacks intrinsic catalytic activity and has been notoriously difficult to study. To address this issue, we leverage novel luciferase technologies to develop and validate 2 split-luciferase biosensor systems that enable accurate quantification of Merlin activity in real time. First, we design an intramolecular biosensor aimed at studying Merlin’s changes in conformation state. In addition, we design a bimolecular split-luciferase system to investigate Merlin’s regulation of the Hippo pathway, a key downstream effector with well-established roles in cancer biology. Ultimately, these biosensors enable improved study of Merlin’s molecular functions, serving as powerful tools to investigate Merlin’s contributions to CIP and tumorigenesis.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution 3.0 United States
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution 3.0 United States