Document Type

Honors Thesis


The Unfolded Protein Response of mitochondria (UPRmt) plays a regulatory role in mitochondrial repair as well as innate immunity. The main transcription factor responsible for regulation of the UPRmt, ATFS-1, mounts a host defense program to counteract infection and promote survival in addition to its function of supporting mitochondrial homeostasis. Among the approximately 400 genes that are regulated by this transcription factor, 23 exhibited features that were reminiscent of antimicrobial peptides (AMP) that act as host defense molecules to fight infection. We used various approaches to test for possible antimicrobial activity of these gene products. We first knocked-down their expression using RNA interference to examine whether this reduced their survival during infection. Second, we tested whether overexpressing each AMP individually in the model organism Caenorhabditis elegans could reduce host colonization of a pathogen. In this approach, we created transgenic animals that express the putative AMP in the intestine. These transgenic animals were then exposed to the pathogen Pseudomonas aeruginosa. The worms were lysed, and colony forming unit counts were performed to evaluate antimicrobial activity. The results concluded that some of these tested peptides may indeed possess antimicrobial properties that promote host resistance.

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