2021-2022 Senior Honors Theses
Permanent URI for this collectionhttps://hdl.handle.net/10657/10473
This collection contains theses produced by Class of 2022 Honors students
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Browsing 2021-2022 Senior Honors Theses by Department "Biology and Biochemistry, Department of"
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Item An Evaluation of Dobzhansky-Muller Incompatibilities in Protein Evolution(2022-05-05) Esopenko, HannahThis study is focused on the evolution of Dobzhansky-Muller Incompatibilities (DMIs) and Compensated Pathogenic Deviations (CPDs) in protein evolution. DMIs are genetic differences that occur by post zygotic isolation to reduce the overall fitness of an organism. Meanwhile, CPDs are pathogenic mutations that show no adverse effects to the organism as there is an additional mutation somewhere in the sequence that compensates for the deleterious nature of the mutation. Therefore, studying the nature of DMIs and CPDs provides a deeper understanding as to how deleterious events arise throughout the evolution of species. A study conducted by Kondrashov et al. (2002) addressed DMIs in protein evolution by identifying the occurrence of CPDs when the nonhuman orthologs deviated from the reference human ortholog sequence. Kondrashov et al.’s (2002) study was clever in construction, but the methodology was unclear, and the results appeared to be over simplified. To analyze the validity of the Kondrashov et al. (2002) paper, a similar study using restricted parameters and modern bioinformatic databases was conducted for this senior thesis project. To do so, 24 primate orthologs of 32 genes responsible for Mendelian diseases were collected and compared to the pathogenic missense data of humans to identify CPDs. Through computational analysis and the visual representation of protein alignments, 26 valid CPD hits were found. The 26 CPD hits presented in four general patterns: single species CPD, single clade CPD with two or more species, convergent evolution of a CPD, and ancestral CPDs. A statistical analysis was performed to determine whether factors such as the length of the protein, the evolutionary distance between sequences, or the number of pathogenic variants played a role in the number of CPDs found. The relationship between the number of CPDs found and the evolutionary distance between sequences and the amount of pathogenic variant data were found to be statistically significantly correlated. More data and research into primate genomes and the nature of CPDs is required to accurately determine their occurrence. This will help predict how CPDs arise in species and better evaluate the claims made in the Kondrashov et al. (2002) paper.Item An Unbiased Approach on The Conformational Dynamics of In-Solution Fibrinogen and Its Physiological Implications.(2022-04-29) Esparza Pinelo, Jose E.By itself, Fibrinogen (Fng) stands out as one of the most complex hematopoietic proteins in the cardiovascular system for multiple species in nature. Upon its activation and further cascade mechanisms, Fng can polymerize into fibrin and contribute to blood clot formation and substantial growth. Fng’s interactions with fibrinolytic proteins aggregate into a conglomerate of different fragments in blood bodily mechanisms. Any form of dysregulation in any of these pathways can lead to several complications not only within the cardiovascular system but throughout the entirety of the body. Understanding the crux of Fng’s functions and interactions with itself along with other proteins ultimately can be traced back to its inherent dynamic structure. In this study, I aim to probe the intrinsic flexibility that is beset on Fng by way of its multi-domain composition, allowing it to withstand incredible mechanical forces as well as being highly dynamic in its physiological form. Thus, extending the key biological concept that structure and flexibility that comes with it determine functions. Through an unbiased approach by implementing protein structural studies as well as computational dynamic simulations, in-solution Fng dynamics were studied in their totality.Item Scaffold Design for Photogrowable Nanonetworks and Pre-Evaluation for Orthogonal Nanoparticle Expansion(2021-12-03) De Vita Sifontes, Giovanna V.A substantial part of polymer chemistry focuses on the formation of block copolymers for functionalization. These polymers possess a wide range of characteristics based on how they are constructed and polymerized. Recently, the focus in this field has shifted to the formation of nanoparticles. Harth’s research group has led the way in creating photogrowable nanonetworks (PGNNs). There is an inherent difficulty in conducting orthogonal expansion polymerizations once a PGNN is formed. The challenge of PGNN is to conduct controlled polymerizations that expand either from the scaffold or crosslinker without affecting each other or any end groups. This project covers the formation of various scaffolds for PGNNs with varying properties, and pre-evaluation polymerization reactions involving symmetrical trithiocarbonate crosslinkers to conduct orthogonal polymerizations on nanoparticles involving these scaffolds and crosslinkers. Scaffolds were constructed using reversible-addition fragmentation chain transfer (RAFT) polymerization, or atom transfer radical polymerization (ATRP). The preliminary reactions that tested the crosslinkers were performed with catalyst ZnTPP under green light and with methyl acrylate as the monomer. Several control reactions were performed to examine the orthogonality of the nanonetwork polymerizations. The construction of the scaffolds provided three different designs for expansion methods and different attachment methods for the crosslinkers. Evaluation tests performed on the crosslinkers demonstrated that orthogonal polymerization can be achieved on a PGNN. This project contributed to the formation of three different design scaffolds for future PGNNs and controlled reactions that demonstrate orthogonal expansion of the individual components of photogrowable networks.