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Advisory Committee Chair

Shahid M Mukhtar

Advisory Committee Members

Asim Bej

Robert W Thacker

Document Type

Thesis

Date of Award

2014

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Entire new molecular worlds of immunity and autoimmunity have been unveiled through the lens of systems biology. Although many believe that vertebrates maintain the most complex immune system, a rival to this concept is arising due to a systems' biology perspective of plant immunity. There are various rising systems biology approaches that unveil this previously uncharted territory. The organization of subjects within systems biology including "-omes" and protein-protein interaction networks enhance such exploration. The field of plant immune network biology is growing alike its parts: prevailing computational modeling approaches of biological regulatory network dynamics, rising technologies and availing research avenues pertaining to the "-omics" approach. Systems biology approaches also pursue clues related to the molecular mechanisms of human autoimmunity, a current mystery. Although the factors that cause the onset of systemic lupus erythematosus (SLE) are not fully understood, it is known to have several genetic risk factors. One factor relates to the fragment crystallizable gamma receptor gene 2B, FCGR2B, that codes for the protein FcgRIIB. FcgRIIB is responsible for maintaining homeostasis within a cell by simultaneously triggering the activation or inhibition of receptors related to undesired autoimmune responses. Systems biology provides effective approaches towards uncovering the role of human fragment crystallizable receptors (FCRs) in autoimmunity. In this thesis, three primary objectives were pursued to expand the knowledge of molecular human autoimmunity: the identification of novel interacting partners of FCRs' cytoplasmic domains; the finding of statistically overrepresented cis-regulatory elements in FCGR2B and identification of their cognate transcription factors; and the identification of FCGR2B CNV (Copy number variation) in SLE patients. The first objective entailed the application of a yeast-two hybrid assay, a high-throughput technology that identified protein-protein interactions and resulted in the generation of the first human autoimmune network. Bioinformatic tools that identify motifs, namely MEME and POBO, were utilized for the second objective. Lastly, the third objective entailed a revamped methodological approach that yielded a full-length RACE PCR product of the 1q23 gene cluster, which is the location of the FCGR2B gene. This full-length product enables the investigation for associations between FCGR2B CNV and SLE onset.

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