Jamieson, Thomas (2023) Chloride intracellular Channel 4 as a therapeutic target in the development of pulmonary arterial hypertension. Master of Science by Research (MScRes) thesis, University of Kent. (doi:10.22024/UniKent/01.02.105785) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:105785)
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Official URL: https://doi.org/10.22024/UniKent/01.02.105785 |
Abstract
Pulmonary Arterial Hypertension (PAH) is a high-mortality disease centred on the progressive dysfunction of the right ventricle, as a result of pulmonary artery lumen narrowing and increased pulmonary vascular resistance. Chloride intracellular channel (CLIC) 4 has been recently suspected to play a role in the development of PAH pathogenesis via the propagation of vascular remodelling, a hallmark of PAH. CLIC4's involvement is linked to a newly-hypothesised CLIC4/Arf6 pathway, involving the protein Arf GTPase-activating protein (GIT) 1. This thesis shows the investigation into CLIC4 interactions with inhibitor Digoxin, and GIT1, which was modelled by assigning CLIC4 residues to a 2D Heteronuclear Single Quantum Coherence (HSQC) NMR spectrum. The results allowed a binding site on CLIC4 to be predicted manually and computationally, and CLIC4-GIT1 interactions were determined which strongly suggests CLIC4:GIT1 interactions in vivo. Overall, this thesis provides evidence of CLIC4's involvement in vascular remodelling pathways, and its viability as a therapeutic target and supports the novel Arf6/CLIC4 pathway believed to propagate PAH development. With this, the study provides new ideas into combatting PAH development, in a bid to reduce PAH-related mortality.
Item Type: | Thesis (Master of Science by Research (MScRes)) |
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Thesis advisor: | Ortega-Roldan, Jose |
DOI/Identification number: | 10.22024/UniKent/01.02.105785 |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
SWORD Depositor: | System Moodle |
Depositing User: | System Moodle |
Date Deposited: | 29 Apr 2024 09:10 UTC |
Last Modified: | 01 May 2024 08:43 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/105785 (The current URI for this page, for reference purposes) |
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