Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 78 for “"Co-receptor"”.
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The role of the CCR5 co-receptor conformation in HIV fusion
This thesis aimed to better define the co-receptor conformation by determining whether mutants of the CCR5 receptor stabilized in the active conformation were less able to mediate HIV fussion. Eight mutant receptors were generated by site-directed mutagenesis and screened for constitutive activity …
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Functional consequences of South African mutations of the HIV-1 co-receptor, CCR5
Four mutations of the CCR5 receptor have been identified in the South African population, but the effects of these mutations on CCR5 function and HIV infection are unknown. We have used in vitro methods to assess the ffect of the mutations, Asp2Val, Leu107Phe, Arg225Gln and Arg225stop, on CCR5 …
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Using genotypic and phenotypic methods to determine the HIV co-receptor phenotype in the clinical setting
… people worldwide. It uses one of two main co-receptors to infect cells. The primary objective of this thesis is to evaluate genotypic and phenotypic assays for co-receptor usage in the clinical setting and investigate approaches for improvement of these assays. Methods: The concordance of …
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The G-protein coupled receptor CMKLR1/ChemR23: Studies on gene regulation, receptor ligand activation, and HIV/SIV co-receptor function
… organisms, there is a need for intercellular communication. G-protein coupled receptors (GPCRs), located on the cell surface, play an important role in this communication. Cells synthesize and release signalling molecules (ligands), which produce a specific response only in those cells that …
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Integrin-independent activation of Tie2 using the de novo designed protein H8mb
… have been limited by the poor developability and receptor promiscuity of Angiopoietin-1 (Ang1), which binds both Tie2 and α5β1 integrin. Here we report the de novo design of a compact Tie2 binding protein that overcomes these constraints. We use RFdiffusion to design a stable, high-affinity Tie2 …
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HEDGEHOG SIGNAL TRANSDUCTION IN EFFECTOR IMMUNE CELLS
… manner and downstream of the T-cell receptor. Whether this pathway is also functionally relevant in NK cells, an innate lymphocyte, has not been fully established. Moreover, the unique adaptations in how Hh signalling is orchestrated in lymphocytes are not well explored. Specifically, …
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Engineering and Characterization of High-Affinity T Cell Receptors
… T cells, as well as T cells expressing the co-receptor CD8. The peptide sensitivity of T cells that expressed the highest-affinity TCRs reached a plateau, suggesting the existence of an affinity maximum for T cell activation. Furthermore, CD8 requirements were directly related to the …
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The Role of T Cell Receptor: Peptide MHC Affinity in T Cell Activation
Engineering of TCRs requires stabilization of the receptor prior to engineering for higher affinity. Chapter 4 details the engineering of a high affinity TCR in its native state, without the need for stabilization, using a T cell display system. T cells bearing the newly isolated TCR bound pepMHC …
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The Role of Type III Transforming Growth Factor-β Receptor in Regulating ALK1 Signaling and Endothelial Biology
… Factor-β (TGF-β) superfamily of ligands and receptors play critical roles in angiogenesis, evidenced by their essential role in physiologic angiogenesis and their perturbation in pathologic angiogenesis. In development, loss or mutation of Activin receptor-Like Kinase 1 (ALK1), an …
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A Novel Gene Therapy Approach Based on Secreted Antiviral Proteins for the Control of HIV Replication
… requires the interaction of the HIV envelope glycoprotein (Env) with a primary receptor (CD4) and a co-receptor (most commonly CCR5 or CXCR4). Protein-based HIV entry inhibitors are highly effective in protecting cells from infection. However, their clinical application is limited because their …
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Protein- hormone interactions patterning the gynoecium
… most intricately patterned organs of the plant, comprisingdifferent tissue sub-structures, all with the purpose of facilitating propagation to the next generation. It is therefore representative of the complexity involved in the initiation and establishment of organ patterning and presents a …
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Characterisation of the Ugandan HIV epidemic with full-length genome sequence data from 1986 to 2016
… D, both subtypes are well established in all cohorts and risk groups, which has facilitated comparison of the two. Previously, HIV sequence data from East Africa has typically been short gene sequences, thus the full-length genome data here has presented an opportunity to compare the …
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Syndecan-4 regulates cell-surface trafficking and biological activity of transglutaminase-2
… in the extracellular matrix (ECM) through an unconventional and not fully understood pathway. Under normal conditions, TG2 modulates cell adhesion, proliferation and tissue repair. Under continuous cell insult higher expression and elevated extracellular trafficking of TG2 contribute to the …
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Genome scale identification of HIV Dependency factors across multiple HIV-1 strains
… and then at a smaller, targeted scale, to uncover novel genes that may act as HIV-1 dependency factors. By using a screening technique which assesses enrichment or depletion of guide based on HIV-1 release from infected cells, I was able to assess the role of host factors across the entire …
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UNDERSTANDING THE INFLUENCE OF TDP-43 LOSS-OF-FUNCTION ON NEUROTROPHIN SIGNALLING
… in neurons affects the proper splicing of the receptor Sortilin resulting in the generation of a soluble isoform. Sortilin functions as a trafficking receptor for neurotrophins and a co-receptor in pro-neurotrophin mediated death, and its soluble form results in reduced activity-dependent …
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Impact of immune activation and inflammation on the susceptibility to HIV infection and disease progression in HIV serodiscordant and seroconcordant couples
The biological correlates of protection against HIV infection remain poorly characterized, hindering the development of an effective prevention strategy. Studies of individuals who resist HIV infection or progress more slowly after being infected are important for the conception of appropriate …
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Rational Identification of Neuropilin-1 Inhibitors: From Deep-Learning to Drug Repurposing
Neuropilins (NRP)—comprising neuropilin-1 (NRP1) and neuropilin-2 (NRP2)—are type I transmembrane glycoproteins with multifunctional extracellular regions. NRP1 functions as a multifunctional, non-enzymatic co-receptor that potentiates signalling from vascular endothelial growth factor (VEGF), …
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Functional Analysis Of A Highly Conserved Cyclin, Cyclin Y, In Drosophila Melanogaster
<p>Cyclin Y is a highly conserved member of the Cyclin superfamily of proteins. In Drosophila the Cyclin Y gene (CycY) is required for progression through several stages of development but the specific pathways that Cyclin Y belongs to and that account for its requirement are not known. Studies in …
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EGFR & HER2 trafficking and signaling dynamics : experimental and modeling studies
… distinguished themselves as important factors in contributing to various types of cancers including breast and ovarian cancers, but quantitative linkages between receptor expression levels and aberrant cell behaviors are not well understood. The ability to interpret and predict cell responses in a …
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Understanding and Engineering Chemically Activated Ubiquitin Ligases for High-throughput Detection, Quantification, and Control of Molecules in Yeast
… aspects of plant growth and defense mechanisms. Conversely, pathogenic fungi can produce auxin and manipulate auxin signaling in their host plant to promote fungal virulence and infection progression. Targeting the auxin signaling pathway in pathogenic fungi offers a novel strategy for combating …
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