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Title: Construction of immune scFv M13 phage display library and isolation of anti-glycan monoclonal antibodies
Author: Saxena, Abhishek
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2013
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As a technology, glycomics could be considered one of the fastest advancing omics disciplines and has provided the potential for greater understanding of molecular and cellular physiology, disease mechanism and therapeutic developments. Glycomics was originally centred on the basic understanding of sugar chemistry and then it evolved to the next level of complexity, when genetic regulation of protein glycosylation was discovered. Despite its importance glycomics has remained something of a neglected area of research and development, partly because it is difficult to study sugars owing to their extreme chemical flexibility. Once thought to be mere structural entities, glycans now serves as prime immunomodulators, being part of the microbial cell, cancer cell surface and even viruses. A brief overview of the general structure of a few common glycans that are highly relevant in the context of fungal infections, and their importance in physiology has been provided. It is evident that due to the rapid advancement in the field of cellular immunology and glycotechnology, a more candid view of host pathogen interface came to the forefront. Recent discoveries of ß-1,3-glucan and mannan, as the prime ligands of dectin-1 and dectin-2 receptors, have imparted a paradigm shift in our understanding of fungal recognition. A particular immunomodulatory profile has been suggested for many of these glycans. Complex glycans are thought to be very important drug targets as the genes involved in sugar assembly are crucial for the synthesis of glycocalyx and more contextually the fungal cell wall. Disruptions of protein functions of one of these factors by small molecule inhibitors were shown to be protective against fungal infections. Also, C. albicans mutant strains that have defects in glycan assembly at the cell surface are significantly less virulent in mouse infection models. These findings directed the evolution of glycan targeting for therapeutic benefits. However, the very idea of targeting glycan does not need to be centred on their physiological importance, but basically to use them as targets of glycan binding proteins and later recruitment of immune elements for faster microbial clearance. Overall growth in the anti-glycan antibody field against fungi and viruses has been tremendous with key molecules moving into advanced pre-clinical stages and early clinical trials. These molecules are already indicated to be a probable commercial success.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Monoclonal antibodies ; Immunotherapy