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M_Varrecchia Dissertation 2017_Final.pdf (5.98 MB)
ETD Abstract Container
Abstract Header
Identification and Characterization of the Forkhead Box Family of Transcriptional Regulators in Parasitic Schistosomes
Author Info
Varrecchia, Melissa M
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=case149728975688442
Abstract Details
Year and Degree
2017, Doctor of Philosophy, Case Western Reserve University, Biology.
Abstract
Schistosomiasis is a disease of global scale with more than 240 million people infected and more than 700 million people at risk of infection. Historically, treatment of this disease has been with one primary drug, praziquantel. Due to this, concern for resistance developing in the parasitic worms that cause this disease has risen. The three species of blood flukes responsible for the majority of the schistosomiasis disease burden are Schistosoma mansoni (S. mansoni), S. japonicum, and S. haematobium. These trematodes have a complex life cycle in which they undergo distinct morphological changes during the transitions from free-swimming to invertebrate and vertebrate host stages. The molecular factors and mechanisms which regulate their development during these metamorphoses are widely unknown. A better understanding of the basic biology of these worms and the factors which drive their development will be critical in the process of identifying new treatment targets or developing preventative measures. Forkhead Box (Fox) proteins, are a family of transcription factors that play key roles in a variety of biological processes including development, metabolism, stress tolerance, and lifespan and have been identified in a number of organisms. The major goal of this thesis is to identify and characterize the complement of forkhead box genes found in the S. mansoni genome. Here, we have identified 15 Fox genes, two with multiple isoforms, which were classified into 11 classes (SmFoxA, SmFoxC, SmFoxD, SmFoxF, SmFoxG, SmFoxJ, SmFoxK, SmFoxL, SmFoxN, SmFoxO, and SmFoxP) using bioinformatics and a phylogenetic comparison to mouse, fly, nematode, and yeast forkhead proteins. Additionally, the expression pattern during the sporocyst, cercarial, 4h schistosomula, and adult stages was determined for each gene using absolute quantitative PCR. To test functionality, SmFox-GAL4 DBD fusion proteins were tested in a modified yeast one-hybrid to determine their ability to activate transcription of the reporter genes HIS3 and MEL1. We determined 12 schistosome Fox proteins are transcriptional activators, though the level of activation varied between proteins and between isoforms of the same protein. This project lays a foundation for the study of schistosome Fox transcription factors and their potential roles in schistosome development.
Committee
Emmitt Jolly (Advisor)
Pages
160 p.
Subject Headings
Biology
;
Parasitology
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Citations
Varrecchia, M. M. (2017).
Identification and Characterization of the Forkhead Box Family of Transcriptional Regulators in Parasitic Schistosomes
[Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case149728975688442
APA Style (7th edition)
Varrecchia, Melissa.
Identification and Characterization of the Forkhead Box Family of Transcriptional Regulators in Parasitic Schistosomes.
2017. Case Western Reserve University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=case149728975688442.
MLA Style (8th edition)
Varrecchia, Melissa. "Identification and Characterization of the Forkhead Box Family of Transcriptional Regulators in Parasitic Schistosomes." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case149728975688442
Chicago Manual of Style (17th edition)
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Document number:
case149728975688442
Download Count:
338
Copyright Info
© 2017, some rights reserved.
Identification and Characterization of the Forkhead Box Family of Transcriptional Regulators in Parasitic Schistosomes by Melissa M Varrecchia is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.
Release 3.2.12