A systems biology approach to target discovery in regulatory T cells

dc.contributor.advisorCauchi, Michael
dc.contributor.advisorPage, Matt
dc.contributor.authorWeston, Marie C.
dc.date.accessioned2024-05-01T13:17:11Z
dc.date.available2024-05-01T13:17:11Z
dc.date.issued2011-08
dc.description.abstractRegulatory T cells (Tregs) have a central role in the maintenance of tolerance to self- antigens and the prevention of autoimmune disease. This study used an integrative systems biology approach to identify tolerogenic genes in Tregs which could potentially serve as novel therapeutic targets for immunological disorders. A consensus Treg gene signature was generated by comparing gene expression in Treg vs naïve or conventional T cells across multiple public studies. Ingenuity Pathway Analysis software was then used to expand the Treg consensus gene list to include interacting proteins accessible to intervention by antibody therapeutics. Many viruses co-opt genes for host proteins that modulate the host’s immune system. It is hypothesized that some viruses may have co-opted genes that can induce tolerance, allowing the virus to evade elimination by the host’s immune system. Putative tolerogenic genes were therefore selected for further investigation based upon their presence in viral genomes. The presence of human genes in viral genomes was investigated by performing a batch reciprocal BLAST search. The biological significance of the human vs viral alignments was evaluated by manual inspection of the alignments and searching for the presence of shared motifs and protein family domains in the viral and human sequences. A final list of ten putative tolerogenic genes included genes known to be associated with immune function and some already established therapeutic targets for autoimmune diseases, as well as four potentially novel therapeutic targets. The biological rationale for the putative targets’ involvement in tolerance was explored in the context of Treg gene expression and protein-protein interaction (PPI) network topology. A PPI network was generated and annotated with confidence scores for each of the interactions. The Cytoscape plugin JActiveModules was used to find putative functional network modules.en_UK
dc.description.coursenameApplied Bioinformaticsen_UK
dc.description.prizeHealth prize winneren_UK
dc.description.sponsorshipBiotechnology and Biological (BBSRC)en_UK
dc.identifier.urihttps://dspace.lib.cranfield.ac.uk/handle/1826/21299
dc.language.isoen_UKen_UK
dc.publisherCranfield Universityen_UK
dc.subjectself antigensen_UK
dc.subjectautoimmune diseaseen_UK
dc.subjectimmunological disordersen_UK
dc.subjectTreg gene signatureen_UK
dc.subjectvirusesen_UK
dc.subjectPutative tolerogenic genesen_UK
dc.titleA systems biology approach to target discovery in regulatory T cellsen_UK
dc.typeThesis or dissertationen_UK
dc.type.qualificationlevelMastersen_UK
dc.type.qualificationnameMScen_UK

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