Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013.

Bibliographic Details
Main Author: Lu, Diana, Ph. D. Massachusetts Institute of Technology
Other Authors: Jeroen P. J. Saeij.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2014
Subjects:
Online Access:http://hdl.handle.net/1721.1/83771
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author Lu, Diana, Ph. D. Massachusetts Institute of Technology
author2 Jeroen P. J. Saeij.
author_facet Jeroen P. J. Saeij.
Lu, Diana, Ph. D. Massachusetts Institute of Technology
author_sort Lu, Diana, Ph. D. Massachusetts Institute of Technology
collection MIT
description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013.
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spelling mit-1721.1/837712019-04-11T10:06:19Z Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15 Lu, Diana, Ph. D. Massachusetts Institute of Technology Jeroen P. J. Saeij. Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology. Biology. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013. Cataloged from PDF version of thesis. In title on title page, "[k̳̳a̳p̳p̳a̳] appear as subscript lower case Greek letter. Page 180 blank. Includes bibliographical references. The apicomplexan protozoan Toxoplasma gondii is an obligate intracellular pathogen that infects all warm blooded animals, including nearly thirty percent of the human population worldwide. Toxoplasma's success as a parasite owes largely to its ability to commandeer its host's immunologic and metabolic processes for its own benefit. During infection, Toxoplasma secretes a large number of proteins into the host cell. Many of these parasite factors modulate the signaling pathways of the host, including the pathway toward NF-[kappa]B activation. The NF-[kappa]B response to infection regulates the direction of host immunity, toward either the classical inflammatory or the alternative non-inflammatory pathway. Using forward genetic analysis, we have isolated the secreted protein GRA 15 that is necessary and sufficient for host NF-[kappa]B activation. We find that GRA 15 activates NF-[kappa]B nuclear translocation and transcriptional regulation in an IKK- and TRAF6-dependent manner. We additionally show that GRA 15 may complex with TRAF3. Some Toxoplasma strains activate the host NF-[kappa]B pathway much more than others. A combination of factors, including differences in expression and sequence of GRA 15, as well as other inhibitory parasite factors are responsible for conferring these strain differences. by Diana Lu. Ph.D. 2014-01-09T19:53:21Z 2014-01-09T19:53:21Z 2013 Thesis http://hdl.handle.net/1721.1/83771 864895118 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 180 pages application/pdf Massachusetts Institute of Technology
spellingShingle Biology.
Lu, Diana, Ph. D. Massachusetts Institute of Technology
Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15
title Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15
title_full Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15
title_fullStr Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15
title_full_unstemmed Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15
title_short Modulation of host NF-[k̳̳a̳p̳p̳a̳]B pathway by the Toxoplasma gondii secreted factor, GRA15
title_sort modulation of host nf kappa b pathway by the toxoplasma gondii secreted factor gra15
topic Biology.
url http://hdl.handle.net/1721.1/83771
work_keys_str_mv AT ludianaphdmassachusettsinstituteoftechnology modulationofhostnfkappabpathwaybythetoxoplasmagondiisecretedfactorgra15