Thesis advisor: Marc-Jan Gubbels / Toxoplasma gondii is an obligate intracellular protozoan parasite capable of invading virtually any nucleated host cell. It is known clinically as the causative agent of toxoplasmosis, a disease that can have disastrous consequences for patients with an impaired immune system or for vertically infected fetuses. Currently available treatments for toxoplasmosis are lacking in long-term efficacy while none target the dormant stage formed by the parasite during infection. Toxoplasmosis results from unchecked completion of the lytic cycle. This cycle is driven by the calcium-dependent processes of host cell invasion and egress. Following a spike in cytoplasmic calcium, apically localized organelles, the micronemes and rhoptries, will secrete their contents and thereby facilitate these events. While much of the signaling pathway leading to microneme secretion is known, there are question marks surrounding microneme trafficking and membrane fusion. Mammalian Ferlins, C2-domain containing proteins, are well-known for facilitating trafficking and membrane fusion events in a calcium-dependent manner. Of the three Ferlin family proteins encoded by T. gondii, FER1 is studied in this thesis. Conditional FER1 overexpression induced premature egress due to an untriggered burst of microneme secretion. Additionally, live imaging micronemes in FER1 overexpressing parasites suggested an additional role for FER1 in trafficking of microneme organelles. Taken together, these data support a role for FER1 in microneme trafficking and the membrane fusion event driving their exocytosis, which are essential for egress, invasion and the successful completion of the lytic cycle. / Thesis (MS) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.
| Identifer | oai:union.ndltd.org:BOSTON/oai:dlib.bc.edu:bc-ir_109280 |
| Date | January 2021 |
| Creators | Drozda, Allison |
| Publisher | Boston College |
| Source Sets | Boston College |
| Language | English |
| Detected Language | English |
| Type | Text, thesis |
| Format | electronic, application/pdf |
| Rights | Copyright is held by the author, with all rights reserved, unless otherwise noted. |
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