Degree Type

Dissertation

Date of Award

2019

Degree Name

Doctor of Philosophy

Department

Veterinary Microbiology and Preventive Medicine

Major

Biomedical Sciences

First Advisor

Timothy Day

Abstract

Schistosomiasis, caused by Schistosoma mansoni, is responsible for infecting approximately 200 million people worldwide, mostly from low-income and middle-income populations; it is a key neglected tropical parasitic disease, second only to malaria as the most devastating parasitic disease in the world. An infection is initiated when the cercarial form of the parasite is released from its intermediary invertebrate host, a Biomphalaria snail, into the surrounding fresh water. Cercariae are non-feeding, free swimming, extremely infectious, highly motile schistosomal stage with bifurcated tails and they penetrate the mammalian skin tail-first, thus infecting the human host. Post attachment, the cercariae sheds its tail and the resulting schistosomule continues to develop within the host circulatory system. The parasites travel to the hepatic system, where they transform into adult worms, mate and lay eggs, most of which are excreted through the host’s excretory system and the rest accumulating within the internal organs of the body. The spread of schistosomiasis relies heavily on the motility of the cercariae before human infection, as well as the movement of the schistosomules through the human body, post infection. For my doctoral dissertation, I have focused on the aspect of motility of the S.mansoni worms pre and post infection. The first part of my research deals with the design and development of a sensitive, simple, cheap biological assay i.e. a microfluidic platform to study the movement of the schistosomules as they travel through the host circulatory system. The complete navigation and the kinetics of the movement of the juvenile worms through the convoluted pulmonary, blood and hepatic vessels within the host remains largely unexplored. We believe that this novel approach will provide a highly efficient method for screening potential anti-schistosomal compounds and improving motility assays. The second part of my research concentrates on the qualitative and quantitative proteomic analysis of the cercarial tails and cercarial bodies. Using mechanical separation of cercarial tails and bodies, and mass spectrometric analyses, we have identified a total of 945 proteins in the combined cercarial proteome from 4 independent samples: 791 proteins in the cercarial tails and 645 proteins from the somule bodies. Gene oncology analysis was conducted on the obtained proteomic data, and the peptide hits were classified based on molecular function, biological function and subcellular location. In conclusion, I believe that by preventing the motility of the parasitic worms at different stages of the life cycle is a novel, previously unexplored route for investigating potential drug targets which could interrupt the spread of the disease.

Copyright Owner

Sreemoyee Acharya

Language

en

File Format

application/pdf

File Size

174 pages

Included in

Cell Biology Commons

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