Barrett, The Honors College Thesis/Creative Project Collection

TSPO was discovered in 1977 and it’s function is still currently unknown. Significant research has suggested that TSPO functions in steroidogenesis to import cholesterol from the mitochondrial outer membrane (MOM) to the mitochondrial inner membrane (MIM) where it is converted into steroids. There were two indications that this is TSPOs main function: its elevated levels in steroidogenic tissue and its primary location in the MOM. There is evidence of TSPO binding cholesterol with high affinity, however there is not currently evidence of TSPO transporting cholesterol. STAR, ACBD1, and ACBD3 are proteins thought to be associated with TSPO and steroidogenesis. However, the distribution of these proteins in various eukaryotes show little similarity suggesting that TSPO functions independently. The function of TSPO in steroid synthesis has been called into question because a well-cited research paper claimed that TSPO knockdown resulted in embryonic lethal mice, however there was no evidence presented from their study and this experiment did not produce the same results when repeated in later studies. There are also studies that show TSPO may not be involved in regulation of sterols, but instead may regulate cell stress. The elevated levels of TSPO during inflammation suggest a role for TSPO in cellular stress. Binding interactions with porphyrins and heme also support that TSPO may modulate stress levels. We used the phylogeny of TSPO in order to gain greater insight into the evolutionary function of TSPO. NCBI BLAST searches revealed that TSPO was present in bacteria and had a widespread but patchy distribution in a small set of eukaryotes. From these initial results, we were prompted to search a larger set of eukaryotes for TSPO. All of the prokaryotic and eukaryotic TSPO sequences were used to create a phylogenetic tree that would provide greater insight into the evolution and function of TSPO. If TSPO was from a common ancestor, it is probable that its function is related to sterol regulation whereas if gained in eukaryotes by horizontal gene transfer from bacteria its function is related to stress regulation. The phylogenetic tree was most consistent with an ancestral origin of TSPO with an evolutionary function related to steroid synthesis regulation. However, there is not sufficient research to confirm the function of TSPO.

The relationship between science and religion in the modern day is complex to the point that the lines between them are often blurred. We have a need to distinguish the two from each-other for a variety of practical reasons. Various philosophies, theories, and tests have been suggested on the interaction between the two and how they are subdivided. One of the sets of criteria which has been shown to work was originally introduced in the opinion of Judge Overton in the case of McLean v Arkansas. McLean v Arkansas is a pivotal case in that it gave us a useful definition of what science is and isn’t in the context of the law. It used the already established Lemon test to show what counts as the establishment of religion. Given the distinction by Judge Overton, there are questions as to whether or not there is even overlap or tension between science and religion, such as in the theory of Stephen Jay Gould’s Nonoverlapping Magisteria (NOMA). What we find in this thesis is that the NOMA principle is doubtful at best. Through the discussion of McLean v. Arkansas, NOMA, and the commentaries of Professors Larry Laudan and Michael Ruse, this thesis develops a contextualization principle that can be used as a guide to develop further theories, particularly regarding the divisions between science and religion.

Cooperative cellular phenotypes are universal across multicellular life. Division of labor, regulated proliferation, and controlled cell death are essential in the maintenance of a multicellular body. Breakdowns in these cooperative phenotypes are foundational in understanding the initiation and progression of neoplastic diseases, such as cancer. Cooperative cellular phenotypes are straightforward to characterize in extant species but the selective pressures that drove their emergence at the transition(s) to multicellularity have yet to be fully characterized. Here we seek to understand how a dynamic environment shaped the emergence of two mechanisms of regulated cell survival: apoptosis and senescence. We developed an agent-based model to test the time to extinction or stability in each of these phenotypes across three levels of stochastic environments.

The study of macaque monkeys harbors advancements in the field of biomedical research. It is imperative to understand the genetic composition of different species of macaques to assess their accuracy as non-human primate (NHP) models for disease detection and treatment assessments. We sought to characterize the hybridization and admixture of the Southeast Asian macaques using single nucleotide polymorphism markers and analyzing the populations on the mainland and the island. Using AMOVA tests and STRUCTURE analysis, we determined that there are three distinct populations: Macaca mulatta, M. fascicularis fascicularis, and M. f. aurea. Furthermore, the island species holds an isolated population of M. f. aurea that demonstrate high inbreeding and genetic uniqueness compared to the mainland species. Findings from this study confirm that NHP models may need to be modified or updated according to changing allelic frequencies and genetic drift.

Cancers of the reproductive tissues make up a significant portion of the cancer burden and mortality experienced by humans. Humans experience several proximal causative carcinogens that explain a portion of cancer risk, but an evolutionary viewpoint can provide a unique lens into the ultimate causes of reproductive cancer vulnerabilities. A life history framework allows us to make predictions on cancer prevalence based on a species’ tempo of reproduction. Moreover, certain variations in the susceptibility and prevalence of cancer may emerge due to evolutionary trade-offs between reproduction and somatic maintenance. For example, such trade-offs could involve the demand for rapid proliferation of cells in reproductive tissues that arises with reproductive events. In this study, I compiled reproductive cancer prevalence for 158 mammalian species and modeled the predictive power of 13 life history traits on the patterns of cancer prevalence we observed, such as Peto’s Paradox or slow-fast life history strategies. We predicted that fast-life history strategists will exhibit higher neoplasia prevalence risk due to reproductive trade-offs. Furthering this analytical framework can aid in predicting cancer rates and stratifying cancer risk across the tree of life.

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.

Pathogenic drug resistance is a major global health concern. Thus, there is great interest in modeling the behavior of resistant mutations–how quickly they will rise in frequency within a population, and whether they come with fitness tradeoffs that can form the basis of treatment strategies. These models often depend on precise measurements of the relative fitness advantage (s) for each mutation and the strength of the fitness tradeoff that each mutation suffers in other contexts. Precisely quantifying s helps us create better, more accurate models of how mutants act in different treatment strategies. For example, P. falciparum acquires antimalarial drug resistance through a series of mutations to a single gene. Prior work in yeast expressing this P. falciparum gene demonstrated that mutations come with tradeoffs. Computational work has demonstrated the possibility of a treatment strategy which enriches for a particular resistant mutation that then makes the population grow poorly once the drug is removed. This treatment strategy requires knowledge of s and how it changes when multiple mutants are competing across various drug concentrations. Here, we precisely quantified s in varying drug concentrations for five resistant mutants, each of which provide varying degrees of drug resistance to antimalarial drugs. DNA barcodes were used to label each strain, allowing the mutants to be pooled together for direct competition in different concentrations of drug. This will provide data that can make the models more accurate, potentially facilitating more effective drug treatments in the future.

Theories about the human origin in evolution and religion are fundamentally countering beliefs that are still debated to this day. This study continues to explore this relationship in the college population at a public university with the intention of targeting a diverse religious population. This research hopes to answer the question: does having greater literacy in evolution lead to a noninterventionist perspective on evolution? The prediction is that evidence of increased evolution comprehension will influence students to have a more agnostic, or noninterventionist, view on evolution. An evolution class was given a survey that had two parts broken into demographic and evolution sections with one question that asks about compatibility between evolution and religion. This was given twice in a single semester to track the growth of evolution knowledge and any other differences. There were 265 students in the initial survey, but only 223 responses in the post-survey. The compatibility question had 8 statements that range from creationist to atheistic perspectives and was divided into two sides: interventionist (divine involvement) and noninterventionist (deity may be present but does not intervene). More than 70% of the class had a noninterventionist perspective on evolution despite the Christian categories being the second largest group students identified with after agnostic. The agnostic statement was the top choice followed by the atheistic answer on the noninterventionist side. Lastly, there was some growth of evolution knowledge for each religious category in the evolution section but is not significant for interpretation. Based on the collected data, it is not sufficient to answer the question and requires more data collection via a longitudinal study.