Identification and therapeutic application of molecular parallels between parasites, parasitic vectors and snake venom

Alghanmi, Maimonah Identification and therapeutic application of molecular parallels between parasites, parasitic vectors and snake venom. Doctor of Philosophy thesis, University of Liverpool.

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Abstract

Neglected tropical diseases (NTDs) are a group of conditions that exert disability and poverty on populations that comprise the world’s poorest billion people. These conditions, although caused by different organisms and cause distinct disease, they share geographical distribution within tropical regions, occur during similar ecological conditions and most importantly have similar biological mechanisms that are utilized to facilitate the pathology of these diseases. Proteolytic enzymes like proteases are used in many biological mechanisms such as, migration through tissue and cellular compartments; haemoglobin digestion, evasion of immune system responses and cause necrosis and fibrosis to vital tissues and organs. Genomic, transcriptomic, and proteomic studies on parasites (S. mansoni and F. hepatica), parasitic vector (An. gambiae) salivary glands and snake venom show that these diverse pathogens appear to be utilizing similar molecules to perform similar biological mechanisms. Therefore, it is of interest to ascertain whether a cross-cutting approach in research could facilitate a better understanding of these diseases. Therefore, the initial aim of this work was to investigate molecular parallels of the mechanisms used by these tropical disease pathogens, including parasites, snake venom toxins, and haematophagic parasite vectors, to access their host’s blood stream. Using a bioinformatics-led approach, in combination with immunological and proteomic analyses, this study demonstrated the presence of similar compounds between shared molecular molecules (serine proteases and other proteins) causing pathology in parasites, parasitic vectors and snake venom. This similarity was not only at the bioinformatics level, but presence of cross-reactivity toward parasite proteins was detected using antivenoms and toxin-specific antibodies. In addition, sera collected from patients infected with S.mansoni exhibited an immune response to snake venom. One of this study aims was to investigate possibilities of using homologous proteins in parasitic vectors and snake venom as therapeutic applications. For this purpose, chimeric epitopes of homologous snake venom (Echis ocellatus) and mosquito salivary proteins were designed as primary vaccine that could be boosted by mosquito bites. If succeeded, this method would prevent, or at least reduce, the devastating pathology and death caused by snake venom at a low cost, with limited logistical complications.

Item Type:	Thesis (Doctor of Philosophy)
Additional Information:	Date: 2014-01 (completed)
Divisions:	Faculty of Health and Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	27 Aug 2014 08:24
Last Modified:	17 Dec 2022 00:13
DOI:	10.17638/00017797
Supervisors:	Harrison, Robert Wagstaff, Simon
URI:	https://livrepository.liverpool.ac.uk/id/eprint/17797