Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(parasite ligand). Showing records 1 – 2 of 2 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Edinburgh

1. Claessens, Antoine. How Plasmodium falciparum malaria parasites bind to human brain endothelial cells.

Degree: PhD, 2011, University of Edinburgh

Cerebral malaria is characterised by an accumulation of infected erythrocytes in the microvasculature of the brain. Plasmodium falciparum infected erythrocytes have been shown to bind to a Human Brain Endothelial Cell line (HBEC-5i) in vitro. This provides a model for the investigation of interactions between P. falcuparum and human brain endothelium. Currently neither the parasite adhesion ligands on infected erythrocytes, nor the host endothelial cell receptors necessary for this interaction have been identified. In this work, the identity of the host receptor on brain endothelial cells was addressed by binding assays of selected and unselected parasites on a wide range of malaria-associated host molecules. The identity of the parasite ligand was investigated by microarray analysis of parasites after selection for cytoadherence to HBEC-5i. The hypothesis being tested was that the gene encoding the parasite cytoadherence ligand would show significant upregulation in selected compared to unselected paarasites. The P. falciparum laboratory strains 3D7, HB3 and IT/FCR3 were selected for binding to HBEC-5i using a panning assay. Compared to unselected parasites, HBEC-5i selected parasites showed a distinct phenotype with reduced platelet-mediated clumping. There was no significant increase in binding of parasites to any of the known endothelial cytoadherence receptors for P. falciparum after selection on HBEC-5i. Binding inhibition assays with various antibodies and soluble receptors did not greatly block the adhesion of parasites to HBEC-5i except for heparin. Altogether, the receptor(s) mediating the interation with HBEC-5i remains unknown. In order to carry out transcriptional analysis of selected and unselected paarasites form all three parasite strains, it was necessary to update the existing microarray chip which is based on the 3D7 genome. This is because each parasite train has a unique repertoire of variant surface antigens (VSAs) including var, rif and stevor genes. Therefore, to fully analysis HB3 and IT genomes. Unique oligonnucleotide probes were then designed for each new sequence and the 3D7-based microarray chip was updated. Transcriptional analysis was then carried out on selected and unselected parasites of all strains. Microarray data clearly indicated that the most highly upregulated genes after selection were group A or group A-like var genes (HB3var3, 3D7_PFDOO2Oc, ITvar7 and ITvar19), showing 11 to over 100 fold upregulation in selected parasites. The rif gene adjacent to the upregulated var gene was also highly expressed. To a lesser extent some exported proteins like RESA-1, PfEMP3 or PHIST family members also showed increased transcription in HBEC-selected parasites (2-3 fold upregulation). Reverse transcriptase-PCR confirmed the upregulation of group A var genes in selected parasites, suggessted that the group A PfEMP1 variants are major candidate ligands for parasite binding to HBEC-5i. These findings are consistent with previous work showing an association between Group A var genes and…

Subjects/Keywords: 616.9883; cerebral malaria; erythrocytes; human brain endothelium; HBEC-5i; parasite ligand; var gene; rif gene; plasmodium falciparum malaria

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Claessens, A. (2011). How Plasmodium falciparum malaria parasites bind to human brain endothelial cells. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/4897

Chicago Manual of Style (16th Edition):

Claessens, Antoine. “How Plasmodium falciparum malaria parasites bind to human brain endothelial cells.” 2011. Doctoral Dissertation, University of Edinburgh. Accessed April 11, 2021. http://hdl.handle.net/1842/4897.

MLA Handbook (7th Edition):

Claessens, Antoine. “How Plasmodium falciparum malaria parasites bind to human brain endothelial cells.” 2011. Web. 11 Apr 2021.

Vancouver:

Claessens A. How Plasmodium falciparum malaria parasites bind to human brain endothelial cells. [Internet] [Doctoral dissertation]. University of Edinburgh; 2011. [cited 2021 Apr 11]. Available from: http://hdl.handle.net/1842/4897.

Council of Science Editors:

Claessens A. How Plasmodium falciparum malaria parasites bind to human brain endothelial cells. [Doctoral Dissertation]. University of Edinburgh; 2011. Available from: http://hdl.handle.net/1842/4897

2. Baradji, Issa. The Role of Apical Membrane Antigen-1 in Erythrocyte Invasion by the Zoonotic Apicomplexan Babesia microti.

Degree: PhD, Veterinary Microbiology, 2010, Texas A&M University

Babesia microti is a tickborne hemoprotozoan parasite that causes the disease babesiosis in humans. Babesia microti Apical Membrane Antigen-1 (AMA-1) is a micronemal protein suspected to play a role in erythrocyte invasion. To investigate interaction between AMA-1 and the host cell, the ectodomain region of the B. microti ama-1 gene was cloned into an expression vector, expressed as a histidine-tagged fusion protein, and used to probe red blood cell membrane proteins in far Western blot assays. The B. microti ama-1 ectodomain, which excludes the signal peptide and the transmembrane region of the open reading frame, was amplified from a cloned gene sequence. The AMA-1 ectodomain is a membrane bound polypeptide that extends into the extracellular space and is most likely to interact or initiate interaction with the host red blood cell surface receptor(s). The amplicon was ligated into a protein expression vector to produce a 58.1 kDa recombinant His-tagged fusion protein, which was confirmed by Western blot analysis. The recombinant B. microti AMA-1 fusion protein was enriched on nickel affinity columns and then used to probe mouse, human and horse red blood cell membrane proteins in far Western blot assays. Babesia microti AMA-1 consistently reacted strongly with a protein migrating at 49 kDa. A similar reaction occurred between the B. microti AMA-1 and horse red blood cell membrane proteins, suggesting that similar interacting proteins of this size are shared by red blood cells from the three species. The B. microti AMA-1 may bind to red blood cell membrane sialic-acid groups, as shown for other Babesia spp. This may explain the signal at the 49 kDa position observed between B. microti AMA-1 and red blood cell membrane proteins from three different species. Further studies may determine if the binding epitopes of the red blood cell binding partner at this position vary and contribute to the specificity of each parasite AMA-1 for their respective host cells. Advisors/Committee Members: Holman, Patricia J. (advisor), Ball, Judith M. (committee member), Magill, Clint C. (committee member), Womack, James E. (committee member).

Subjects/Keywords: Babesia microti; Apical Membrane Antigen-1; AMA-1; erythrocyte; parasite ligand; red blood cell; receptor; protein-protein interaction

…conservation indicates that this ligand plays an essential role in parasite functions (Triglia… …erythrocyte invasion by this parasite. In this study, interaction of the BmAMA-1 ectodomain ligand… …parasites and the characteristic features of this parasite ligand, such as a transmembrane domain… …genera indicate the importance of the role played by this parasite ligand in invasion (… …Parasite Ligands Involved in Invasion of Host Cell . III 7 8 10 11 11 EXPRESSION PLASMID… 

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Baradji, I. (2010). The Role of Apical Membrane Antigen-1 in Erythrocyte Invasion by the Zoonotic Apicomplexan Babesia microti. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/ETD-TAMU-2008-08-68

Chicago Manual of Style (16th Edition):

Baradji, Issa. “The Role of Apical Membrane Antigen-1 in Erythrocyte Invasion by the Zoonotic Apicomplexan Babesia microti.” 2010. Doctoral Dissertation, Texas A&M University. Accessed April 11, 2021. http://hdl.handle.net/1969.1/ETD-TAMU-2008-08-68.

MLA Handbook (7th Edition):

Baradji, Issa. “The Role of Apical Membrane Antigen-1 in Erythrocyte Invasion by the Zoonotic Apicomplexan Babesia microti.” 2010. Web. 11 Apr 2021.

Vancouver:

Baradji I. The Role of Apical Membrane Antigen-1 in Erythrocyte Invasion by the Zoonotic Apicomplexan Babesia microti. [Internet] [Doctoral dissertation]. Texas A&M University; 2010. [cited 2021 Apr 11]. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2008-08-68.

Council of Science Editors:

Baradji I. The Role of Apical Membrane Antigen-1 in Erythrocyte Invasion by the Zoonotic Apicomplexan Babesia microti. [Doctoral Dissertation]. Texas A&M University; 2010. Available from: http://hdl.handle.net/1969.1/ETD-TAMU-2008-08-68

.