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Tretina_umaryland_0373D_10785.pdf  (26.4 MB)  
Authors: Tretina, Kyle
Advisors: Silva, Joana C.
Date: 2016
Abstract: Intracellular pathogens have evolved intricate mechanisms to subvert host signaling pathways and ensure their own propagation. The protozoan parasite Theileria parva infects bovine lymphocytes, induces host cell proliferation, and synchronously divides with it, segregating into both host daughter cells. Since an accurate compendium of parasite gene structures is critical to understanding the unique biology of this parasite, we used the first RNAseq dataset generated for the schizont parasite life cycle stage and significantly updated the annotation of the parasite genome. This more accurate annotation informed valuable insights into parasite transcriptional gene regulation, which could be valuable to future re-annotation and basic biology research. In order to leverage these data toward investigating host-pathogen interactions, we used transcriptomics, comparative genomics, and surface plasmon resonance to discover that a key enzyme in isoprenoid biosynthesis in T. parva, TpGcpE, also moonlights as a host mitogen by binding to host tumor suppressor retinoblastoma-1 (RB). We show in vitro that TpGcpE impedes binding of endogenous epigenetic regulators to RB. We show that the TpGcpE-RB interaction also prevents RB complexes from repressing both E2F transcription factor activity and downstream host proliferation ex vivo. The pleiotropic role of GcpE has enabled the evolution host cell transformation in the phylum Apicomplexa, a path uniquely followed by the transforming Theileria species.
Subject Keywords: Cancer
Theileria parva--genetics
Theileria parva--pathogenicity
Description: University of Maryland, Baltimore. Molecular Microbiology and Immunology. Ph.D. 2016
Type: dissertation
Appears in Collections:Theses and Dissertations Graduate School
Theses and Dissertations School of Medicine

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