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- All Subjects: 2 hybrid system
- Creators: Shi, Yixin
Description
Colorectal cancer is the third most common type of cancer that affects both men and women and the second leading cause of death in cancer related deaths[1, 2]. The most common form of treatment is chemotherapy followed by radiation, which is insufficient to cure stage four cancers[3]. Salmonella enteric has long been shown to have inherent tumor targeting properties and have been able to penetrate and exist in all aspects of the tumor environment, something that chemotherapy is unable to achieve. This lab has developed a genetically modified Salmonella typhimurium (GMS) which is able to deliver DNA vaccines or synthesized proteins directly to tumor sites. These GMS strains have been used to deliver human TNF-related apoptosis inducing ligand (TRAIL) protein directly to tumor sites, but expression level was limited. It is the hope of the experiment that codon optimization of TRAIL to S. typhimurium preferred codons will lead to increased TRAIL expression in the GMS. For preliminary studies, BALB/c mice were subcutaneously challenged with CT-26 murine colorectal cancer cells and treated with an intra-tumor injection with either PBS, strain GMS + PCMV FasL (P2), or strain GMS + Pmus FasL). APC/CDX2 mutant mice were also induced to develop human colon polyps and treated with either PBS, strain GMS + vector (P1), P2, or P3. The BALB/c mouse showed statistically significant levels of decreased tumor size in groups treated with P2 or P3. The APC/CDX2 mouse study showed statistically significant levels of decreased colon polyp numbers in groups treated with P3, as expected, but was not significantly significant for groups treated with P1 and P2. In addition, TRAIL was codon optimized for robust synthesis in Salmonella. The construct will be characterized and evaluated in vitro and in vivo. Hopefully, the therapeutic effect of codon optimized TRAIL will be maximal while almost completely minimizing any unintended side effects.
ContributorsCrawford, Courtney Rose (Co-author) / Crawford, Courtney (Co-author) / Kong, Wei (Thesis director) / Shi, Yixin (Committee member) / Fu, Lingchen (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Porphyromonas Gingivalis (P.G.) is a gram-negative anaerobic bacillus that is commonly implicated in periodontal disease in humans via invasion of oral epithelial cells. Characterizing the intracellular mechanisms that allow for these infections to take place is important for future attempts to stop or halt the spread of infection. Given the complexity of bacterial virulence, research on the subject often necessitates precise measurements of very specific biochemical pathways. In this study, we focus on the type IX secretion system utilized by P.G. to initiate colonization of host cells. Specific to this secretion system is the PorX-PorY two-component regulatory system. Here we use the bacterial adenylate cyclase based 2 hybrid system to test if two specific domains of the PorX-PorY system communicate intracellularly with each other; and hence gain further knowledge on how this infection occurs.
ContributorsKrautz, Zackary (Author) / Shi, Yixin (Thesis director) / Lynch, John (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor)
Created2024-05