Analysis of the Allergenic Potential of the Ubiquitous Airborne Fungus Alternaria Using Bioinformatics

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dc.contributor.authorBabiceanu, Mihaelaen
dc.contributor.committeechairLawrence, Christopher B.en
dc.contributor.committeememberBevan, David R.en
dc.contributor.committeememberLi, Liwuen
dc.contributor.committeememberSetubal, João C.en
dc.contributor.departmentGenetics, Bioinformatics, and Computational Biologyen
dc.date.accessioned2016-09-22T15:14:47Zen
dc.date.adate2011-07-14en
dc.date.available2016-09-22T15:14:47Zen
dc.date.issued2011-06-15en
dc.date.rdate2009-03-04en
dc.date.sdate2011-06-21en
dc.description.abstractAmong the environmental airborne fungi one of the most common is <i>Alternaria alternata</i>. From a clinical perspective Alternaria has long been associated with IgE-mediated, histamine-dependent mold allergy, allergic rhinitis, chronic rhinosinusitis (CRS) and asthma. Recently it has been proven that an abnormal immunological response to Alternaria most likely contributes to the pathogenesis of upper respiratory airway disorders. In this body of work, we present for the first time results of several sets of experiments including, 1) the analysis of A. alternata spore germination expressed sequence tags (ESTs), 2) the survey of global allergen homologues in fungal genomes, and 3) the first microarray experiment investigating airway epithelial cell responses to this fungus. In the first project, the analyses of the EST dataset offered a first look into the gene content of A. alternata and represents the beginning of future research of this ubiquitous fungus. Annotation and classification of ESTs revealed a number of genes that could be involved in the immunomodulation process of the human immune response toward fungi. We also discovered that the majority of known allergens are expressed during the spore germination phase of A. alternata. For investigating the allergenic potential of fungi we developed a whole genome approach by querying fungal genome sequences (<i>A. alternata, A. brassicicola,</i> and <i>Aspergillus fumigatus</i>) with a database of all known allergenic proteins from a taxonomically diverse group of organisms. Interestingly, we identified homologues of diverse types of allergens in these fungal genomes and also many homologues of allergens from other organisms including those from pollen, insects, and venoms. Finally, we investigated global gene expression changes of human airway cells in response to <i>A. alternata</i> and an ∆alt a 1 deletion mutant. We found that wild type Alternaria spores induced significant changes in gene expression patterns in human airway epithelial cells, especially known immune response genes. Furthermore, results of these analyses revealed that Alt a 1 is a major factor in inducing epithelial inflammatory responses.en
dc.description.degreePh. D.en
dc.identifier.otheretd-06212011-114739en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-06212011-114739/en
dc.identifier.urihttp://hdl.handle.net/10919/73007en
dc.language.isoen_USen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectAlt a 1en
dc.subjectAlternariaen
dc.subjectallergenen
dc.titleAnalysis of the Allergenic Potential of the Ubiquitous Airborne Fungus Alternaria Using Bioinformaticsen
dc.typeDissertationen
dc.type.dcmitypeTexten
thesis.degree.disciplineGenetics, Bioinformatics, and Computational Biologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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