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- Creators: Hindemith, Paul, 1895-1963
Description
Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great efforts to get a properly attenuated Salmonella vaccine strain for a long time, but could not achieve a balance between attenuation and immunogenicity. So the regulated delayed attenuation/lysis Salmonella vaccine vectors were proposed as a design to seek this balance. The research work is progressing steadily, but more improvements need to be made. As one of the possible improvements, the cyclic adenosine monophosphate (cAMP) -independent cAMP receptor protein (Crp*) is expected to protect the Crp-dependent crucial regulator, araC PBAD, in these vaccine designs from interference by glucose, which decreases synthesis of cAMP, and enhance the colonizing ability by and immunogenicity of the vaccine strains. In this study, the cAMP-independent crp gene mutation, crp-70, with or without araC PBAD promoter cassette, was introduced into existing Salmonella vaccine strains. Then the plasmid stability, growth rate, resistance to catabolite repression, colonizing ability, immunogenicity and protection to challenge of these new strains were compared with wild-type crp or araC PBAD crp strains using western blots, enzyme-linked immunosorbent assays (ELISA) and animal studies, so as to evaluate the effects of the crp-70 mutation on the vaccine strains. The performances of the crp-70 strains in some aspects were closed to or even exceeded the crp+ strains, but generally they did not exhibit the expected advantages compared to their wild-type parents. Crp-70 rescued the expression of araC PBAD fur from catabolite repression. The strain harboring araC PBAD crp-70 was severely affected by its slow growth, and its colonizing ability and immunogenicity was much weaker than the other strains. The Pcrp crp-70 strain showed relatively good ability in colonization and immune stimulation. Both the araC PBAD crp-70 and the Pcrp crp-70 strains could provide certain levels of protection against the challenge with virulent pneumococci, which were a little lower than for the crp+ strains.
ContributorsShao, Shihuan (Author) / Curtiss, Roy (Thesis advisor) / Arizona State University (Publisher)
Created2012
ContributorsHindemith, Paul, 1895-1963 (Composer)
DescriptionA novel and unconventional approach for delivering a eukaryotic apoptosis factor, TNF-related apoptosis-inducing ligand (TRAIL), to cancer cells within and around necrotizing tumors by utilizing a S. Typhimurium purine requiring auxotroph as a biological vector to develop two anticancer therapies with multiple modality and broad economic feasibility.
ContributorsKoons, Andrew (Author) / Curtiss, Roy (Thesis director) / Lake, Douglas (Committee member) / Janthakahalli, Nagaraj Vinay (Committee member) / Barrett, The Honors College (Contributor)
Created2013-12
Description
Coronaviruses are a significant group of viruses that cause enteric and respiratory infections in a variety of animals, including humans. Outbreaks of Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) in the past 15 years has increased research into coronaviruses to gain an understanding of their structure and function so one day therapies and vaccines may be produced. These viruses have four main structural proteins: the spike, nucleocapsid, envelope, and membrane proteins. The envelope (E) protein is an integral membrane protein in the viral envelope that acts as a viroporin for transport of cations and plays an important role in pathogenesis and viral assembly. E contains a hydrophobic transmembrane domain with polar residues that is conserved across coronavirus species and may be significant to its function. This experiment looks at the possible role of one polar residue in assembly, the 15th residue glutamine, in the Mouse Hepatitis Virus (MHV) E protein. The glutamine 15 residue was mutated into positively charged residues lysine or arginine. Plasmids with these mutations were co-expressed with the membrane protein (M) gene to produce virus-like particles (VLPs). VLPs are produced when E and M are co-expressed together and model assembly of the coronavirus envelope, but they are not infectious as they do not contain the viral genome. Observing their production with the mutated E protein gives insight into the role the glutamine residue plays in assembly. The experiment showed that a changing glutamine 15 to positive charges does not appear to significantly affect the assembly of the VLPs, indicating that this specific residue may not have a large impact on viral assembly.
ContributorsHaller, Sarah S. (Author) / Hogue, Brenda (Thesis director) / Liu, Wei (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor) / Biodesign Institute (Contributor)
Created2017-05
Description
Identifying disease biomarkers may aid in the early detection of breast cancer and improve patient outcomes. Recent evidence suggests that tumors are immunogenic and therefore patients may launch an autoantibody response to tumor associated antigens. Single-chain variable fragments of autoantibodies derived from regional lymph node B cells of breast cancer patients were used to discover these tumor associated biomarkers on protein microarrays. Six candidate biomarkers were discovered from 22 heavy chain-only variable region antibody fragments screened. Validation tests are necessary to confirm the tumorgenicity of these antigens. However, the use of single-chain variable autoantibody fragments presents a novel platform for diagnostics and cancer therapeutics.
ContributorsSharman, M. Camila (Author) / Magee, Dewey (Mitch) (Thesis director) / Wallstrom, Garrick (Committee member) / Petritis, Brianne (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor) / Virginia G. Piper Center for Personalized Diagnostics (Contributor) / Biodesign Institute (Contributor)
Created2012-12
Description
The purpose of my honors thesis project was to generate the tools needed for in vivo imaging by determining the optimal plasmid-fluorophore combination. To determine the optimal plasmid and fluorophore, asd plasmids were constructed with various promoters, origins of replications, and red fluorophores. The optimal asd plasmid for fluorescent in vivo imaging was determined by the plasmid stability, growth rate, and growth phase dependence on fluorescent intensity. The end goal is to be able to use the asd plasmid in vaccine strains for the purpose of in vivo imaging of the recombinant attenuated Salmonella vaccine (RASV).
ContributorsEudy, L. Adam (Author) / Curtiss, Roy (Thesis director) / Roland, Kenneth (Committee member) / Forbes, Stephen (Committee member) / Barrett, The Honors College (Contributor) / College of Liberal Arts and Sciences (Contributor)
Created2012-12
ContributorsHindemith, Paul, 1895-1963 (Composer)
ContributorsHindemith, Paul, 1895-1963 (Composer)
ContributorsHindemith, Paul, 1895-1963 (Composer)
ContributorsHindemith, Paul, 1895-1963 (Composer)