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Utilizing interspecies comparisons between Toxoplasma gondii and Hammondia hammondi to elucidate mechanisms driving life stage development, life cycle flexibility, and pathogenesis

Sokol Borrelli, Sarah (2021) Utilizing interspecies comparisons between Toxoplasma gondii and Hammondia hammondi to elucidate mechanisms driving life stage development, life cycle flexibility, and pathogenesis. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Multi-host life cycles of eukaryotic parasites are fundamentally important for their success because they are linked to the way that these parasites replicate, disseminate, transmit, and cause disease in each host. As parasites of this nature progress through their life cycle, they transition between different developmental stages that function to promote survival and transmission in a specific host environment. The transitions between these life stages are especially important for the parasites Toxoplasma gondii and Hammondia hammondi. T. gondii and H. hammondi are closely related Apicomplexans that share a large majority of their genes in near perfect synteny. Despite this genomic similarity, these parasites have stark differences in their life cycle flexibility and virulence. To begin to understand the mechanisms for these differences, we have compared the developmental programs of these parasite species in head-to-head experiments and identified critical differences in the timing of stage conversion and response to stress. We were able to exploit this knowledge to produce the first ever transgenic H. hammondi line. We also used the developmental differences between T. gondii and H. hammondi and thorough transcriptional comparisons to identify new factors driving life stage conversion in T. gondii. Specifically, we identified the gene Regulator of Cystogenesis 1 (ROCY1), which encodes a zinc finger CCCH motif containing protein that plays a critical role in in vitro tissue cyst formation and is required for tissue cyst formation in vivo. Our data also suggest that ROCY1 is regulated, at least in part, by a T. gondii transcription factor that serves as a regulator of differentiation, Bradyzoite-Formation Deficient 1 (BFD1). Together, our findings begin to elucidate the regulatory networks driving stage conversion in T. gondii and H. hammondi.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Sokol Borrelli, Sarahsls212@pitt.edusls212
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairBoyle,
Committee MemberBerman,
Committee MemberCarlson,
Committee MemberLee,
Committee MemberSullivan Jr,
Date: 8 October 2021
Date Type: Publication
Defense Date: 7 July 2021
Approval Date: 8 October 2021
Submission Date: 23 June 2021
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 197
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Toxoplasma gondii, Hammondia hammondi, bradyzoite, tissue cyst
Date Deposited: 08 Oct 2021 19:14
Last Modified: 08 Oct 2021 19:14


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