Life Sciences Commons^™

Cd46 Isoforms And Viral Receptor For Adenovirus Type 64d, Corina Stasiak

Honors Theses

Adenovirus Type 64 (Ad.64) belongs to the adenovirus subgroup D, which causes epidemic keratoconjunctivitis (EKC), otherwise known as viral pink eye. There is currently no known effective treatment for EKC. Membrane Cofactor Protein (CD46) is an integral membrane glycoprotein that, in previous studies, has been identified as a protein receptor for the closely related Ad.37. It has been determined that Ad.64 uses CD46 as a receptor on the cell surface in HeLa cells. CD46 is alternatively spliced when expressed to have different isoforms of interest, including the BC and C isoforms. Certain cell types, like A549 lung carcinoma cells, express …

Cd46 Is A Protein Receptor For Human Adenovirus Type 64, Alexander Michael Robertson

Honors Theses

Adenoviruses are important gene delivery vectors and causative agents for a variety of human diseases such as the common cold and gastrointestinal infections. Human adenovirus type 64 (Ad64; formerly 19c) and type 37 are associated with epidemic keratoconjunctivitis. Based upon its high homology and similar disease tropism to Ad37, we hypothesized that Ad64 would have the same protein receptor, CD46 (membrane cofactor protein), as Ad37. We show that a recombinant Ad64 containing an enhanced Green Fluorescent Protein transgene (Ad64.eGFP) enters Chinese hamster ovary cells expressing human CD46 (CHO-CD46) on the surface. Entry into human cervical carcinoma (HeLa) cells is increased …

Development Of A Diaryl Oxazole-Based Cleavable Linker For Peptides, Evan Wolff

Honors Theses

The development of new cleavable linkers increases the diversity of compatible conditions for peptide discovery platforms. Potential applications for these linkers include high-throughput pharmaceutical candidate screening when utilized in Peptide Encoded Libraries (PELs). This thesis describes the development of a bifunctional diaryl oxazole-based cleavable linker that may be incorporated into compounds through Solid-Phase Peptide Synthesis (SPPS). This oxazole-based linker may be rapidly cleaved by cerium ammonium nitrate in aqueous conditions and is compatible with most natural amino acids and a variety of unnatural amino acids. This linker represents the first single-electron oxidant labile linker described to our knowledge and it …

Structural Phylogenetics Of A Family Dna Polymerases, Yagmur Bingul

Honors Theses

The transition from the RNA to the DNA world stands as an important event, demanding the emergence of enzymatic activities for DNA precursor synthesis, retro-transcription of RNA templates, and replication of single and double-stranded DNA molecules. The distribution of protein families associated with these activities across the three domains of life—Archaea, Eukarya, and Bacteria—adds layers of complexity to the narrative. While Archaea and Eukarya often share similar protein structures, structural biology shows homologous, but distinct, structures in Bacteria. On the other hand, viral polymerases emerge as a crucial part of genome replication and transcription. Their versatility, including RNA-dependent RNA polymerase, …

Functionalized Gold Nanoparticles And Halogen Bond Interactions With Neonicotinoid Pesticides, Molly Mccuen “Mackey” Sherard

Honors Theses

Neonicotinoid (NN) pesticides have emerged globally as one of the most widely used agricultural tools for protecting crops from pest damage and boosting food production. Unfortunately, some NN compounds, such as extensively employed imidacloprid-based pesticides, have also been identified as likely endangering critical pollinating insects like honey bees. To this end, NN pesticides pose a potential threat to world food supplies. As more countries restrict or prohibit the use of NN pesticides, tools are needed to effectively and quickly identify the presence of NN compounds like imidacloprid on site (e.g., in storage areas on farms or pesticide distribution warehouses). This …

Heterocycles As Peptide-Based Cleavable Linkers, John Blobe

Honors Theses

As cancer cases continue to rise, the need for advancing the treatment options for cancer is ever increasing. Current cancer therapeutics, while effective at treating localized cancers and a fraction of advanced cancers, generally lack the specificity needed to target more advanced cancers. Recent advancements in cancer treatments have leveraged antibodies to target certain cancers. A class of drugs that utilize antibodies to deliver anti-cancer therapy preferentially to cancer cells, termed antibody-drug conjugates (ADCs), have been quite effective in treating certain advanced forms of certain cancers. These ADCs could be more effective if they could allow for the facile release …

Diaryl Oxazoles As Cleavable Linkers For Drug Discovery Platforms, Elizabeth Taggart

Honors Theses

Within the field of medicine and pharmacology, discovering small molecule or biologic based molecules with therapeutic potential is a difficult task. Current methods involve individually screening hundreds of compounds on a potential target biomolecule, and recent technologies have explored peptide encoded libraries (PELs) as a means of making this screening process more high-throughput. These libraries produce a large number of small molecule drug candidates each conjugated to a unique peptide fragment, functioning as a barcode. Analysis of PELs requires the capture of hit small molecules and the subsequent release of their peptide tags; however, current approaches are limited in their …

Investigation Of The Vira Linker Domain To Characterize Its Phenol Interactions, Jessica Garofalo

Honors Theses

The soil bacterium Agrobacterium tumefaciens causes tumors in plants through interkingdom gene transfer. This transfer is initiated upon a wounding event that results in the release of plant signaling factors such as phenols and sugars that are recognized by protein machinery in the periplasm and inner membrane of A. tumefaciens. The histidine kinase protein VirA, in combination with the periplasmic protein ChvE, recognizes these signals and initiates induction of virulence genes via a signaling pathway, culminating with the insertion of tumor-inducing T-DNA into the wounded plant cells. While the interaction between the Periplasmic domain of VirA and sugar-bound ChvE …

Role Of Cdx4 And Sp5l In Zebrafish Development, Wesley Tsai

Honors Theses

The Caudal Type Homeobox transcription factors cdx are a family of genes found in vertebrates that regulates body regionalization and anterior-posterior patterning. They are also responsible for regulating axial elongation, but the mechanisms behind this behavior are not known. Previous studies in mouse embryonic stem cells have shown that the cdx genes are necessary for upregulating the gene sp5 which may be linked to axial elongation. Sp5 is a zinc-finger transcription factor belonging to the specificity protein (sp) family. Our group has used in-situ hybridization experiments on zebrafish embryos to show that sp5-like (sp5l) is transcribed within tailbud tissues that …

Bryophytes Of Goochland County, Virginia, Mikayla Quinn

Honors Theses

Bryophytes are non-vascular land plants that include mosses, liverworts, and hornworts. Although easier to overlook because of their smaller size, bryophytes are a fundamental part of the ecosystem. As such, maintaining record of their biodiversity is important. Yet, records of bryophyte species in Goochland County, VA were low compared to more thoroughly documented counties such as Prince Edward County. This study expands the documentation of bryophyte flora and presents a checklist of bryophyte species found Virginia’s Goochland County from 2020-2023. Fieldwork conducted at public and privately-owned properties throughout the county between January 2020 and March 2023 yielded 702 specimens that …

Electrochemical Reduction Of Carbon Dioxide Using Ruthenium And Amines, Sydney Moise

Honors Theses

With an increased concern for climate change in the recent years, a significant area of research has been devoted to the reduction of greenhouse gases. Carbon dioxide (CO2) resides in the atmosphere between 300 – 1000 years, making the reduction of the molecule a substantial field of study.1 Amines have been used as CO2 scrubbing agents in literature historically, due to their ability to form bonds to carbon.2 Although studies involving metal catalysts and amines have been reported numerous times, research involving chemical reduction of CO2 using purely amines is scarce. In this paper, amines, in addition to hydride donors …

Investigating The Helicase Activity Of Methylated Vs Unmethylated Ded1, Hannah Lukow

Honors Theses

Ded1 is an RNA helicase protein of the DEAD-box subfamily in eukaryotic organisms (Sharma & Jankowsky, 2014) which can act as an activator or initiation factor, during translation (Hilliker et al., 2011). Ded1 has several functions in yeast including assembly of translational initiation factors, scanning the mRNA for the start codon, and unwinding any double stranded segments of mRNA with its helicase ability. Ded1 was discovered to be methylated at four arginine sites in vivo (Low et al., 2013), with a fifth methylation site being discovered recently (Low et al., 2020), however the purpose of such post-translational modifications is still …

Analysis Of Wild Rodent Gut Microbiota As A Function Of Exposure To Ticks And Tick-Borne Pathogens, Joshua Pandian

Honors Theses

Due to advances in high-throughput parallel sequencing, researchers have conducted novel studies exploring relationships between microbiome compositions and different aspects of organism health. Some of these studies have shown that the gut microbiome of rodent models has effects on organism health and behavior and that infection with pathogens and the composition of the skin microbiome are linked to changes in gut microbiome composition. While previous studies have shown how vector microbiota impact vector behavior and pathogen transmission, the effect vectors have on reservoir species microbiomes has been a less prominent focus. We were interested in the relationships between tick parasitism, …

The Role Of Cerium(Iii) In Bacterial Growth And The Microbial Transformation Of Aromatic Hydrocarbons, Shruti Sathish

Honors Theses

Biofilms are communities of surface-attached bacterial cells encased in an exopolymeric matrix. In this state, they are more resistant to antimicrobial treatment and can have adverse effects in medical, agricultural, and industrial settings. Whereas, as biocatalysts, biofilms from nonpathogenic bacteria enhance their performance and stability in catalysis. Unfortunately, there are several challenges when using bacteria in organic transformations due to their complex cellular chemistry. Trivalent lanthanide metals were discovered to serve regulatory roles in some bacterial catalytic processes, including those of Pseudomonas putida KT2440 (P. putida), a non-infectious Gram-negative bacterium. The main goal of our research is to use cerium(III) …

Halogen Bonding: A Computational Chemistry Investigation Of The Interaction Between Thyroid Hormone And Deiodinase, William Rice

Honors Theses

Halogen bonding is a noncovalent interaction that continues to garner interest among the scientific community. Investigation of halogen bonds in biological contexts typically revolves around rational drug design for developing therapeutics. However, halogen bonding may be occurring naturally in our body every day. Thyroid hormone and its regulating enzyme, iodothyronine deiodinase, show promising results for a halogen bonding interaction that happens during catalysis. Prior work has examined the interaction between the iodine of thyroid hormone and the selenium of iodothyronine deiodinase. However, this study is the first of its kind to use computational chemistry methods to analyze the halogen bond …

Investigation Of The Effects Of Resveratrol And Epigallocatechin Gallate On Woodsmoke-Induced Inflammation, Sarenna Naomi Enright

Honors Theses

Until a few years ago, most scientific investigations related to the health effects of air pollution focused on outdoor air pollutants. But in recent years, the concerns over indoor air pollution has increased. People can spend up to 90% of their time in indoor environments, especially their homes, even more so since the beginning of the COVID-19 pandemic. The concentrations of some air pollutants are five times higher than what is found outdoors.

Indoor air pollution exposure remains a significant cause of morbidity and mortality worldwide. Approximately half of the global population is exposed to abnormally high concentrations of household …

Research Towards Understanding Hox Regulation By Cdx, Joshua M. Fisher

Honors Theses

In this project, we aim to functionally test the contribution that individual Cdx binding sites have in hox gene regulation. We will achieve this by individually blocking Cdx binding sites using CRISPR/dCas9 in the zebrafish and then analyzing changes in the time, distribution, and levels of hox gene transcription.

We will focus our analysis in only one of the seven zebrafish hox clusters, the hoxca cluster. We are focusing on the hoxca gene cluster because it has lost the least number of genes relative to other clusters and is involved in specifying the axial identity of cells in …

Investigation Of The Effects Of Curcumin On Woodsmoke-Induced Inflammation, Melissa Lewis

Honors Theses

Inflammatory diseases caused by biomass smoke exposure and indoor air pollution affect millions of people worldwide. These diseases can be caused by the burning of biomass (plastic, wood, rubber, tobacco, etc.) for light or heat. Acrolein is a common indoor and outdoor pollutant from tobacco smoke or organic combustion. Wood smoke is hypothesized to cause inflammation since it contains high concentrations of particulate matter and gaseous compounds and are similar in size to other well-known damaging particles. Natural remedies, like curcumin, are hypothesized to be a natural remedy for combating inflammation. The goal of this research was to investigate the …

The Effect Of Color Morph On Behavior Interactions In Red-Backed Salamanders (Plethodon Cinereus), Taylor M. Aliferis

Honors Theses

Studies in behavioral ecology provide critical information regarding a species’ territoriality, predator-prey interactions, and reproduction. Red-backed salamanders (Plethodon cinereus) are a polymorphic terrestrial amphibian whose behavioral interactions have long been studied to provide insights on the processes that structure salamander populations, which are often cryptic and difficult to study. However, research regarding the effect of coloration on these interactions is more limited, but potentially extremely important for studies of population dynamics and speciation in terrestrial salamanders. In this study, aggressive and submissive behaviors of adult male red-backed salamanders in five different color morph treatment pairings were observed to …

The Effects Of Signaling Molecules To Agrobacterium Tumefaciens Tumorigenesis At Plant Wound Sites, Nicole Walker

Honors Theses

Agrobacterium tumefaciens can live independently within soil before infecting its host (McCullen and Binns, 2006). The bacterium infects the plant through the rhizosphere, an area of soil along the plant root surface which contains microorganisms, making up the “external metabolome” (Bais et al. 2006). As these bacteria live in the rhizosphere, they are exposed to a multitude of chemical signals. These chemical signals include several conditions that must be met before the virulence machinery is expressed. These conditions include signaling from phenols and sugars as well as low PO4 levels and low pH. Upon wounding, sugars and phenols are released …

The Influence Of Flooding On Macroinvertebrate Diversity Of The James River Rock Pools, Meghan Leber

Honors Theses

Biodiversity within an ecosystem can be greatly influenced by environmental disturbances, such as fires, flooding, or other extreme events. Studying the effects of these disturbances on species diversity can be complicated though, due to difficulties tracking species-level responses and isolating the effects of disturbances. Model systems in community ecology, such as rock pools, are a beneficial way to scale down the study of disturbances in discrete communities without losing the ability to analyze important influences or interactions. In this study, macroinvertebrates within the James River rock pools were surveyed to investigate seasonal and annual differences in species richness and diversity, …

Application Of Β-Chloroenals: One-Pot Syntheses To Create Highly Variable, Functional, And Biologically Interesting Molecules, Julia Powell Siewert

Honors Theses

Pyrroles and pyrazoles are privileged structures which provide a molecular framework found in many different classes of bioactive compounds, thus rendering their syntheses useful in pharmaceutical drug development. Additionally, being able to selectively create these molecules with interesting substituents allows for different pharmacological and biological activities, such as antitumor and antibiotic effects. Our group has used β-chloroenals in the application of many different unique synthetic strategies in the past, and here I show that chloroenals can be used to synthesize novel 1,2,5 trisubstituted pyrroles as well as 1,5 di- and 1,4,5 trisubstituted pyrazoles in fewer steps and with milder conditions …

Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque

Honors Theses

Non-Celiac Gluten Intolerance (NCGI) has evaded biological and chemical mechanisms since it was first reported in 1978. Celiac Disease, a multi-system immune mediated disorder has long served as the most similar counterpart to NCGI. Less cases of celiac disease are going undiagnosed reflecting an improvement on sensitive and decisive diagnostic tools. However, NCGI has been significantly growing as a diagnosis over the past decade with little match or similarity to the markers found in celiac disease patients. Critical evaluation of NCGI theories, experimentation, and existing hypotheses is necessary. This review seeks to synthesize multiple disciplines of gluten research and enhance …

What Lies Beneath? : Removal Sampling To Test For Biases In Surface Activity Of The Eastern Red-Backed Salamander (Plethodon Cinereus), Amelia Tedesco

Honors Theses

In light of the current global amphibian extinction crisis from threats such as climate change and disease, reliable and repeatable sampling methods carry heavy importance for assessing North American salamander species.

Bartonella And Y. Pestis Screening In Ctenophyllus Armatus Terribilis For Conservation Application For The America Pika (Ochotona Princeps) In The Rocky Mountain Front Range, Hilary Rinsland

Honors Theses

As temperatures continue to disproportionally increase in alpine regions due to climate change, parasite spillover from increased pika-rodent contact could bring new diseases to a susceptible alpine specialist, the American pika (Ochotona princeps). Fleas collected from pika at four alpine and subalpine study sites in Boulder County, Colorado from 2011-2017 were screened for Y. pestis and Bartonella using conventional PCR methods. This is the first study to detect Bartonella in the American Pika flea Ctenophyllus armatus terribilis and to propose the presence of B. grahmii in the alpine region of the Rocky Mountains.

Characterizing Borrelia Burgdorferi In Virginia : Lyme Disease Prevalence As A Matter Of Bacterial Genetic Variation, Hannah Cornman

Honors Theses

yme Disease (LD) incidence and spatial distribution has grown dramatically in the past 20 years. In Virginia, the growth has been especially drastic, primarily in the Western part of the state. This research project investigates how genetic variability of the Lyme Disease causing bacteria, Borrelia burgdorferi, might be contributing to this increase in LD incidence in western Virginia. To do this, B. burgdorferi samples were isolated from ticks found across the state and were characterized by multilocus sequence typing (MLST). Phylogenetic and minimum spanning tree analyses were also performed. It was hypothesized that the increasing number of Lyme disease infections …

Understanding The Structural Basis Of Sike Interactions, Alice Catalano

Honors Theses

Tank Binding Kinase 1 (TBK1) acts as a catalytic hub in the regulation of numerous immune signaling pathways. Suppressor of IκB Kinase ε (SIKE) was recently characterized as a substrate of TBK1 whose binding properties are modulated by phosphorylation state, but very little is currently known about its function. However, because SIKE is known to form a dimer with itself, previous work generated a list of potential SIKE partners based on other proteins that contain sequences homologous to SIKE. Here, computational models of four potential SIKE partners, Heavy Chain myosin, tubulin, Beta Catenin and Ezrin, were generated and docked with …

Interactions Between Two Key Amphibian Defenses To Batrachochytrium Dendrobatidis In Panamanian Glass Frogs (Espadarana Prosoblepon), Andi Levorse

Honors Theses

Research on the amphibian pathogen Batrachochytrium dendrobatidis (Bd), the causative agent of the lethal disease chytridiomycosis, has advanced from assessments of pathogenicity and species susceptibility to more specialized questions concerning the complex interactions between the pathogen, species-specific immune responses, and the environment. Our work examines the potential for interactions between the two most important innate immune defenses of frogs against Bd: secretions of antimicrobial peptides and communities of commensal cutaneous bacteria. While both defenses have been studied individually, little data are available to examine interactions between these defenses. We conducted our study with field captured Panamanian glass frogs …

Community Structure Of The Microbiome Of Ixodes Scapularis In Relation To Sex, Stage, Lineage, And Geography, Christopher Lee Clark

Honors Theses

This study sought to fill these gaps of knowledge ticks as a model species. Based on the known information on the microbiome of vectors, and ticks more specifically, I sought to answer two prominent questions: are there relationships between the microbiome of individual ticks and do ticks from different sexes or life stages have variance in their microbiomes? In reference to my first question, I hypothesized that ticks coming from the same lineage, being the males, 7 Community Structure of the Microbiome of Ixodes scapularis females, and resulting eggs, would have a more similar microbiome to each other than to …

The Progression Of Lyme Disease In The State Of Virginia, Margaret Michel

Honors Theses

Lyme disease has spread in the United States from the northeast to more southern and western parts of the country. It has been shown that the tick which most often carries the Lyme disease pathogen (Borrelia burgdorferi) in North America, Ixodes scapularis, has also spread to these new areas of concern. In Virginia, the disease has progressed from the eastern shore to the western, more mountainous regions. Through obtaining historical museum specimens of mice from 11 locations in Virginia, we seek to determine whether the Lyme disease causing pathogen, B. burgdorferi, has always been present in …