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Identifying a role for heat shock proteins in Schistosoma mansoni

Ishida, Kenji
http://rave.ohiolink.edu/etdc/view?acc_num=case1496938244172559

Abstract Details

2017, Doctor of Philosophy, Case Western Reserve University, Biology.
Parasitic schistosome worms infect more than 240 million people worldwide, causing the debilitating disease, schistosomiasis. The primary drug for treatment, praziquantel, has been used for decades, with rising concern for drug resistance. Therefore, a better understanding of the biology of schistosomes is necessary to identify targets for the development of novel chemotherapeutics. In this thesis, we describe experiments involving heat shock genes and proteins performed in Schistosoma mansoni, one of the main species responsible for human schistosomiasis. From the understanding that schistosomes undergo many environmental transitions during their six-stage, two-host lifecycle, we can reason that heat shock response may play a vital role in helping the parasite survive these transitions. The studies here focus on the role of the heat shock transcription factor and heat shock proteins in cercariae, the infective stage for the mammalian host. First, we characterized the heat shock transcription factor (SmHSF1) using several methods. A modified yeast 1-hybrid assay verified the ability of SmHsf1 to activate transcription. In a bandshift DNA-binding assay, recombinant purified SmHsf1 demonstrated specific binding to DNA oligonucleotides containing sequences corresponding to those from the region upstream of schistosome heat shock protein 70 (gene, HSP70) and of the heat shock consensus sequence. Transcript analysis by quantitative PCR of cDNA from several parasite stages showed constitutive expression of SmHSF1. Using a custom-raised antibody, Western blotting showed bands specific for SmHsf1, and immunohistochemical staining of cercaria stage parasites showed a novel localization of SmHsf1 to the acetabular glands. In the subsequent study, we focused on the role of heat shock protein 70 (protein, Hsp70), which is a downstream effector protein of the Hsf1 transcription factor, in cercaria stage parasites. Treatment of cercariae with an Hsp70 inhibitor led to a shift in swimming behavior, similar to the treatment of cercariae with human skin lipid, indicating that Hsp70 may be a key mediator of the host sensing and invasion process. Taken together, the studies presented here implicate for the first time, to our knowledge, an important role for heat shock response-associated proteins during the development of the infective cercaria stage and mammalian host invasion in schistosomes.
Emmitt Jolly, Ph.D. (Advisor)
Michael Benard, Ph.D. (Committee Chair)
Ronald Blanton, M.D./M.Sc. (Committee Member)
Christopher Cullis, Ph.D. (Committee Member)
Claudia Mieko Mizutani, Ph.D. (Committee Member)
155 p.
Biology
Schistosoma; Schistosoma mansoni; schistosomes; schistosomiasis; cercaria; heat shock; Hsf; acetabular glands; Hsp; invasion; honing

Recommended Citations

Citations

  • Ishida, K. (2017). Identifying a role for heat shock proteins in Schistosoma mansoni [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1496938244172559

    APA Style (7th edition)

  • Ishida, Kenji. Identifying a role for heat shock proteins in Schistosoma mansoni. 2017. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1496938244172559.

    MLA Style (8th edition)

  • Ishida, Kenji. "Identifying a role for heat shock proteins in Schistosoma mansoni." Doctoral dissertation, Case Western Reserve University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1496938244172559

    Chicago Manual of Style (17th edition)

case1496938244172559
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© 2017, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.