Biological studies of GPI-anchoring in Trypanosoma cruzi

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Biological studies of GPI-anchoring in Trypanosoma cruzi

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dc.contributor.advisor Nisha J. Garg en_US
dc.creator Michele Anne Zacks en_US
dc.date.accessioned 2011-12-20T16:04:50Z
dc.date.available 2009-06-09 en_US
dc.date.available 2011-12-20T16:04:50Z
dc.date.created 2007-07-03 en_US
dc.date.issued 2007-04-24 en_US
dc.identifier.other etd-07032007-110046 en_US
dc.identifier.uri http://hdl.handle.net/2152.3/140
dc.description.abstract Trypanosoma cruzi, a protozoan parasite transmitted to humans via triatomine\r\ninsects, causes chronic chagasic cardiomyopathy (CCM) in ~30% of infected individuals.\r\nThis dissertation sought to characterize T. cruzi’s pathogenic mechanisms by cellular,\r\nbiochemical, and molecular genetics approaches. In several protozoans, including T.\r\ncruzi, dominant cell surface proteins are attached to the parasite membrane by\r\nglycosylphosphatidylinositol (GPI) anchors and play roles in host cell attachment and\r\ninvasion, and in parasite differentiation and replication. In other organisms, a\r\ntransamidase, GPI8, is involved in this anchoring process. This study investigated the\r\neffects of protein-GPI depletion on T. cruzi growth and development by over-expressing\r\nTcGPI8 mutated in putative active site residues, which were determined based on\r\nsignificant homology to other GPI8s and plant endopeptidases containing conserved Cys\r\nand His residues in their active sites. In T. cruzi expressing TcGPI8 mutant alleles\r\n(C198A or H156A), no alteration in GPI-anchoring efficiency or impairment of in vitro\r\ninfectivity, differentiation or replication was observed. These results indicate that\r\nTcGPI8’s active site may not be comprised of H198A and C156A and, therefore, differs\r\nfrom that of yeast, human and Leishmania GPI8. Alternatively, targeted disruption of\r\nTcGPI8 in T. cruzi was employed to provide protein-GPI deficient mutants. Unintended\r\ndisruption of the GAPDH gene resulted from this approach and marked growth and\r\ndevelopmental defects were observed in these parasites at the epimastigote stage. en_US
dc.format.medium electronic en_US
dc.language.iso eng en_US
dc.rights Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. en_US
dc.subject molecular parasitology en_US
dc.subject life cycle en_US
dc.subject en_US
dc.title Biological studies of GPI-anchoring in Trypanosoma cruzi en_US
dc.type.material text en_US
dc.type.genre dissertation en_US
thesis.degree.name PhD en_US
thesis.degree.level Doctoral en_US
thesis.degree.grantor The University of Texas Medical Branch en_US
thesis.degree.department Experimental Pathology en_US
dc.contributor.committeeMember Robert A. Davey en_US
dc.contributor.committeeMember Paul J. Boor en_US
dc.contributor.committeeMember David H. Walker en_US
dc.contributor.committeeMember Ashok K. Chopra en_US
dc.contributor.committeeMember Anant K. Menon en_US

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