Theses and Dissertations

Hundreds of thousands of people die annually from malaria; a protozoan of the genus Plasmodium is responsible for this mortality. The Plasmodium parasite undergoes several life stages within the mosquito vector, the transition between which require passage across the lumen of the mosquito midgut. It has been observed that in about 15% of parasites that develop ookinetes in the mosquito abdomen, sporozoites never develop in the salivary glands, indicating that passage across the midgut lumen is a significant barrier in parasite development (Gamage-Mendis et al., 1993). We aim to investigate a possible correlation between passage through the midgut lumen and drug-resistance trends in Plasmodium falciparum parasites. This study contains a total of 1024 Anopheles mosquitoes: 187 Anopheles gambiae and 837 Anopheles funestus samples collected in high malaria transmission areas of Mozambique between March and June of 2016. Sanger sequencing will be used to determine the prevalence of known resistance alleles for anti-malarial drugs: chloroquine resistance transporter (pfcrt), multidrug resistance (pfmdr1) gene, dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr). We compare prevalence of resistance between abdomen and head/thorax in order to determine whether drug resistant parasites are disproportionately hindered during their passage through the midgut lumen. A statistically significant difference between resistance alleles in the two studied body sections supports the efficacy of new anti-malarial gene surveillance strategies in areas of high malaria transmission.

In completing this thesis project, I attempted to hypothesize the trigger in my own personal diagnosis of type 1 diabetes through literature research as well as further research on viruses and their contribution to autoimmune disorders. I had previously hypothesized that, based on my own family life, type 1 diabetes could possibly be a non-heritable disease despite its consistent inheritance pattern discovered by researchers; however, the research presented in this thesis project rejects this idea and supports the theory that I may have been previously susceptible to this disorder and would have developed type 1 diabetes naturally. There were multiple viruses discovered during the literature research conducted that could possibly have been triggers in the acceleration of my disease. The major link between enteroviruses and autoimmune disorders was discovered, as well as influenza A and SARS-COV-2 and this is explained further in this project.

Cells have mechanisms in place to maintain the specific lipid composition of distinct organelles including vesicular transport by the endomembrane system and non-vesicular lipid transport by lipid transport proteins. Oxysterol Binding Proteins (OSBPs) are a family of lipid transport proteins that transfer lipids at various membrane contact sites (MCSs). OSBPs have been extensively investigated in human and yeast cells where twelve have been identified in Homo sapiens and seven in Saccharomyces cerevisiae. The evolutionary relationship between these well-characterized OSBPs is still unclear. Reconstructed OSBP phylogenies revealed that the ancestral Saccharomycotinan had four OSBPs, the ancestral Holomycotan had five OSBPs, the ancestral Holozoan had six OSBPs, the ancestral Opisthokont had three OSBPs, and the ancestral Eukaroyte had three OSBPs. Our analysis identified three clades of ancient OSBPs not present in animals or fungi.