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Title: Synthetic protein scaffolds as tools for detection and modulation of lectin-like oxidised low-density lipoprotein receptor 1
Author: De Siqueira, Jonathan Reynolds
ISNI:       0000 0004 7964 3710
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2018
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Lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) is a type E scavenger receptor found on the walls of endothelial cells, platelets, macrophages and smooth muscle cells among others. Technologies for sensing and inhibiting LOX-1 are limited to poorly performing antibodies and genetic knockouts and despite significant correlation with poor clinical outcomes, no LOX-1 modulation therapy has been tried in man. This thesis aims to establish whether 'Affimers'; new, small-size antibody mimetics can be used in an assay platform to detect soluble forms of LOX-1 in solution and in the modulation of its function as an oxLDL receptor. The findings show that Affimers can be used in combination with antibodies, or in complimentary binding pairs to develop a sensitive chemiluminescence based assay. Further, when used in a concentration of 500ng/ml, Affimers can inhibit the early binding of oxLDL to LOX-1, in a controlled LOX-1 cellular expression system, though their effect is nulled after prolonged incubation. Such findings along with other recently published evidence demonstrate that Affimers show great promise as diagnostic and therapeutic agents and there is enormous opportunity to develop the technology further from bench to bedside.
Supervisor: Ponnambalam, Sreenivasan ; Homer-Vanniasinkam, Shervanthi ; Russell, David Alexander Sponsor: Leeds Vascular Institute Charitable Fund
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available