Browsing by Subject "viruses"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Development and Applications of Gold Nanoparticles and Elastomeric Polymers as Biomaterials(2021-07) Siehr, AllisonThis thesis is focused on the development and applications of two different types of biomaterials: nanoparticles and polymers. In chapter 1, I briefly review these biomaterials. In chapter 2, we develop gold nanoparticles (GNPs) that can be driven to either self-assemble or remain colloidally stable using coiled-coil protein interactions. Control over the GNP self-assembly or stability is critical for specific biomedical applications. In chapter 3, we use the self-assembling GNPs to inhibit human immunodeficiency virus type-1 (HIV-1) by adding a targeting ligand for HIV-1. However, we found our GNPs are weak inhibitors of HIV-1. Methods to improve the inhibitor design are then discussed. In chapter 4, a biomaterials-based approach is used to elucidate the structures of HIV-1 and human T-cell leukemia virus type-1 (HTLV-1). A GNP immunolabeling strategy is used to identify HIV-1 and HTLV-1 envelope proteins, critical for viral entry and targets for vaccine development. However, the immunolabelling strategy was not robust, and alternative methods to study envelope proteins are discussed. Lastly, in chapter 5, a novel elastomeric polymer is evaluated for biomedical applications. PLA-PβMδVL-PLA polymers were synthesized in this work and shown to exhibit elastomeric properties. Next, the polymers were found to be biocompatible and biodegradable both in vitro and in vivo. Overall, this thesis demonstrates the development and applications of both gold nanoparticles and elastomeric polymers as biomaterials.Item Overlapping functions of APOBEC enzymes in antiviral immunity and cancer(2017-07) Starrett, GabrielAPOBEC enzymes are a family of innate antiviral enzymes that form an important barrier against DNA-based pathogens. Encoding and expressing these DNA mutating enzymes, however, is an inherently risky endeavor for the stability of the host genome if not regulated appropriately. These risks have been demonstrated in numerous cancers where APOBEC3B is overexpressed and the APOBEC-associated mutation signature is enriched. Emphasizing the importance of this observation, elevated expression of APOBEC3B and presence of APOBEC-associated mutations has now been consistently linked to aggressive phenotypes and worse outcome in cancer patients. Here I present data demonstrating overlapping functions of APOBEC3 enzymes in antiviral immunity and cancer. In both of these models, APOBEC3 enzymes contribute potentially deleterious and beneficial mutations potentially impacting the survival of tumors and viruses. Additionally, the functions of these enzymes can be modulated by heritable germline mutations in the APOBEC3 locus and viral infections. DNA viruses can also act as valuable molecular probes into the regulation of APOBEC3 enzymes in tumors leading to the development of better therapies.