Biochemistry, Biophysics, and Structural Biology Commons^™

Shark Immunology And Its Biomedical Potential: Evolution, Innovation, And The Imperative Of Conservation, Reesha Bhagat

Undergraduate Honors Thesis Collection

This review aims to shed light on a significant ecological deficit and its implications for the future of science and medicine. Sharks possess a uniquely adaptive, cancer-resistant, and evolutionarily refined immune system with transformative biomedical potential, making their conservation a scientific and medical imperative. We are losing something medically irreplaceable, and we don’t even fully understand it yet. Shark conservation is a pressing scientific imperative because sharks are ecologically essential and represent an irreplaceable biomedical resource.

Sequence Determinants Of Rna G-Quadruplex Unfolding By Arg-Rich Regions, Naiduwadura Ivon Upekala De Silva, Puspa Kunwar, Md Ibnul Rifat Rahman, Joanna Koryo Kwao, Nathan Lehman, Zihan Zhang, Trenton Paul, Claire Cheng, Nicholas Truex, Hui-Ting Lee, Jun Zhang

Faculty Publications

RNA sequences with the potential to form G-quadruplexes (rGQs) are widespread but largely unfolded in cells by unknown mechanisms. rGQ folding status is a critical regulator of RNA splicing and translation. We show that rGQs can be unfolded by SR proteins, SR-related proteins, and other Arg-rich proteins, including SRSF1, SRSF3, SRSF9, U1-70K, and U2AF1. The length and composition of Arg-rich regions are key determinants of this activity: Arg residues are the primary drivers, while acidic residues attenuate the unfolding activity. To unfold ARPC2 rGQ, at least 13 Arg residues are required. Our findings identify Arg-rich proteins as previously unrecognized, helicase-independent …

Evaluation Of Flt3 Inhibition With Quizartinib During Busulfan Conditioning For Hematopoietic Stem Cell Transplantation, Catherine Jankovic

Biochemistry and Molecular Biology

Hematopoietic stem cell transplantation (HSCT) is one of the only curative therapy options for many hematologic malignancies. HSCT relies on effective conditioning regimens to deplete host hematopoietic cells and enable donor engraftment. The alkylating agent Busulfan is widely used in myeloablative conditioning strategies due to its potent cytotoxic effects on hematopoietic cells and ability to clear the bone marrow. However, optimization of conditioning strategies remains an important area of investigation to improve transplant outcomes and reduce toxicity. Preliminary studies have shown that the FLT3 inhibitor Quizartinib synergizes with some chemotherapeutic agents, suggesting that targeted inhibitors may enhance conventional conditioning regimens. …

Analysis Of Developmental Cardiogenic Processes Mediated By Fox And Zinc-Finger Transcription Factors, Rajnandani Katariya

All-Inclusive List of Electronic Theses and Dissertations

Cardiogenesis is a highly choreographed biological process requiring the precise integration of gene regulatory networks to govern cell division, fate determination, and spatial positioning. Disruptions in these mechanisms lead to congenital heart defects (CHDs), which affect approximately 1% of live births globally. Due to the evolutionary conservation of cardiac signaling pathways and the structural homologies between the Drosophila dorsal vessel and the early vertebrate heart tube, Drosophila melanogaster serves as a powerful model for dissecting the fundamental mechanisms of heart development. This dissertation investigates the molecular orchestration of cardiac development, specifically focusing on the roles of the transcription factors Jumu …

Reconstruction Of Fox Transcription Factor-Regulated Subnetworks Mediating Cardiac Progenitor Cell Divisions, Md Rezaul Hasan

All-Inclusive List of Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly worldwide, affecting approximately 1% of live births, corresponding to 1.35 million infants born with CHD each year, and remains a leading cause of infant mortality; therefore, it is urgent to understand the genetic and molecular mechanisms underlying CHD for advancing early diagnosis and treatment. Because many aspects of the Drosophila heart formation are highly reminiscent of vertebrate heart development, Drosophila melanogaster serves as a simple yet powerful model system for studying cardiac development and CHD. While at least eight Forkhead box (Fox) transcription factors (TFs) are required for proper cardiac …

Analysis Of The Effects Of Astaxanthin On Human Colorectal Cancer Cells, Kara A. Walters

Theses/Capstones/Creative Projects

Astaxanthin (AXT) is an antioxidant carotenoid that is produced by the microalgae Haemococcus pluvialis. This supplement is best known for its potential health benefits including anti-inflammatory, antitumor, immunomodulatory, anticancer and antidiabetic activities. Astaxanthin is marketed as an oral dietary supplement and is widely used in the nutraceutical industry as well as a coloring agent in the food industry. Since Astaxanthin has been increasingly popular as a dietary supplement, cytotoxicity is relevant to consumer exposure. Obtaining the IC50, the concentration that inhibits 50% of cell growth, is important to find how Astaxanthin may interact with cancer, and this can be found …

Acute Effects Of The Psychoactive Pollutant Fluoxetine On The Antipredator Behavior Of The Gulf Killifish (Fundulus Grandis), Semyra Reus

Honors Theses

Pharmaceutical contaminants are increasingly prevalent in aquatic environments, yet their sublethal effects on ecologically relevant behaviors remain poorly understood, particularly in estuarine systems. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are of particular concern due to the conserved role of serotonin in regulating behavior across vertebrates. Here, we investigated how acute exposure to environmentally relevant concentrations of fluoxetine influences anti-predator behavior in Gulf killifish (Fundulus grandis), a key estuarine fish commonly found in saltmarsh habitats. Killifish were exposed to control (0 ng/L), low (17.8 ng/L), and high (596 ng/L) fluoxetine concentrations and subsequently tested in the presence …

Novel Biomarker Discovery In Multiple Sclerosis, Manisha Gangasani

Honors Theses

Multiple Sclerosis (MS) is a chronic neuroinflammatory disorder affecting the brain, spinal cord, and optic nerve. Patients experience cognitive, motor, autonomic, and emotional symptoms that often overlap with other neurological conditions, making early diagnosis challenging. Current diagnostic criteria require evidence of lesions with dissemination in time and space. Racial disparities in MS outcomes are well documented, with Black individuals often exhibiting greater disease severity, higher relapse rates, and increased disability compared to White individuals. These differences likely reflect a combination of genetic, biological, environmental, and healthcare access factors, underscoring the need to improve early diagnosis and reduce inequities in care. …

Developing A Protocol For Non-Cellular Transplantation Of Donor Mitochondria Into Recipient Cells, Andrew Parton

Honors Theses

Tumor innervation has emerged as a critical feature of cancer progression, with increased nerve density correlating with enhanced aggressiveness, metastatic dissemination, and poor clinical outcome. However, the functional contribution of neurons to tumor biology remains incompletely defined. We recently identified the intercellular transfer of mitochondria from neurons to cancer cells as a mechanism that promotes tumor progression. We therefore hypothesized that disruption of this transfer could attenuate tumor aggressivity. To directly investigate this process, we developed an approach to isolate mitochondria from donor cells and transplant them into recipient cancer cells independently of canonical cell-cell interactions. Transferred mitochondria were tracked …

Understanding Tlr3 Immune Response Activation In Cryptosporidium Parvum And Cryspovirus Pathogenesis, Surayya Hudayberganova

Biochemistry and Molecular Biology

Cryptosporidiosis is a serious gastrointestinal illness caused by a protozoan parasite known as Cryptosporidium. It is particularly dangerous for malnourished children and those with compromised immune systems. My research focuses on the Toll-like receptor 3 (TLR3) response to the Cryptosporidium parvum infection, specifically in the presence of the parasite’s viral mutualist named cryspovirus (CSpV1). Results using research methodologies like ELISA and RT-qPCR have indicated that TLR3 expression increases during the infection process of Cryptosporidium parvum (C. parvum). Furthermore, one intriguing observation concluded during this study suggests that administering the TLR3-specific inhibitor CU-CPT4a to infected cells drastically decreased this activation. This …

College Of Natural Sciences Spring Newsletter, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

[Page 1] Dean's Message
[Page] 2 Awards & Recognitions // Student Spotlights
[Page] 3 Zhang Named to Landsat Science Team // The Power of Teaching
[Page] 4 “Science as Art” Competition Welcomes High School Artists
[Page] 5 Testing for “Forever Chemicals” in Surface Water // New Faculty Spotlight
[Page] 6 Ambassador Initiated Outreach
[Page] 7 57th Annual Geography Convention
[Page] 8 Twice the Impact on On Call with the Prairie Doc
[Page] 9 Making Staple Foods Healthier // Halaweish & Cole-Dai Retire
[Page] 10 Drone Day 2026
[Page] 11 Student Research, Scholarship, and Creative Activity Day (SRSCAD)
[Page] 12 Ceremony …

Unveiling The Biochemical Pathway Responsible For Ankyloglossia (Tongue-Tie) By Tracking Enzymatic Activity Of Apoptosis Pathways, Becca Ringstad

Celebrating Scholarship and Creativity Day (2018-)

Ankyloglossia (Tongue-tie) is a condition that is caused by failed cellular degeneration leading to a short lingual frenulum. This short lingual frenulum tethers the tongue to the bottom palate of the mouth and leads to problems, including breastfeeding for infants, depriving them of important proteins that build the gut microbiome, strengthen the immune system, and fight off antigens. If left untreated, it leads to problems with speech articulation, airway development, and obstructive sleep apnea. Treatment involves a frenectomy, which is the release of the short lingual frenulum using surgical scissors or a laser. Ankyloglossia can occur with conditions such as …

Genome-Wide Phenotypic Characterization Of Mycobacteriophage Mercurio, Tyler Downs

Departmental Honors & Graduate Capstone Projects

Bacteriophages, or phages, are being piloted as a supplemental or alternative therapeutic to antibiotics against drug-resistant Mycobacterium pathogens, such as M. tuberculosis, which pose a global public health crisis.  Characterizing bacteriophage genomes can provide insights into efficacy in phage therapy before implementation or elucidate new targets to manipulate bacterial growth.  Overexpression of individual phage genes is useful to study a gene product’s function independent of others.  Here, the results of phage Mercurio plasmid library overexpression in plate-based assays are described.  Mercurio infects nonpathogenic Mycobacterium smegmatis and is genetically related to bacteriophages infecting pathogenic Mycobacterium species.  Eleven gene products of …

Phenotypic Contribution And Regulation Of Vibrio Parahaemolyticus Cold-Shock Protein Homologue Vp1889, Oleg Borisovich Ermolinsky

Theses and Dissertations

Vibrio parahaemolyticus is the primary causative agent of a form of gastroenteritis called vibriosis commonly acquired from ingestion of raw and undercooked seafood. The primary mitigation of seafood-borne illnesses is immediate storage on ice following catch, which inhibits bacterial metabolism and replication. Mesophilic bacteria such as V. parahaemolyticus induce expression of cold-shock proteins in a process named the cold shock response, which facilitates survival at low temperatures. V. parahaemolyticus bears 3 homologues of the major Escherichia coli cold-shock protein CspA, an RNA chaperone. Induction of E. coli CspA at low temperatures depends on autogenous modulation by its mRNA structure, which …

Ethanol State-Dependent Learning In The Honey Bee (Apis Mellifera), Ethan Neil Govea

Theses and Dissertations

Ethanol disrupts neural circuits involved in addiction and withdrawal, yet the molecular mechanisms underlying these effects remain poorly understood. One possibility is that ethanol alters an animal’s perceptual or internal state, causing a stimulus learned while intoxicated to be processed differently when the animal is sober. This study examined how ethanol exposure affects odor learning, recall, and discrimination in honey bees, a useful model because of their robust olfactory learning and experimentally accessible neural systems. Bees were differentially conditioned with appetitive reward (sucrose) during hexanol exposure and aversive stimulus (quinine) during decanol exposure. To assess olfactory processing and state dependency, …

Identification Of Peptides For A Muc13 Cancer Vaccine, Abigail Olivia Gomez

Theses and Dissertations

Mucin 13 (MUC13) is a transmembrane glycoprotein that is frequently overexpressed in epithelial cancers. Its extracellular domains and cytoplasmic signaling potential contribute to disrupted cell adhesion, increased invasion, and cancer-promoting pathways, making MUC13 a promising target for immunotherapy. This project used an in-silico approach to identify MUC13-derived peptides predicted to bind HLA class I molecules and support CD8+ T cell-mediated immune responses. Bioinformatics tools were used to screen candidate epitopes for HLA binding affinity, antigenicity, toxicity, IFN-γ-inducing potential, and population coverage, allowing rational prioritization of peptide candidates for experimentation. Selected peptides were evaluated in THP-1-derived macrophages using RT-PCR, Western blotting, …

Comparative Biomechanics: Blattodea Antennal Morphology And Physiology, Lucas W. Marsh

All Theses

Equipped with muscle-free antennae, many insects can twist and bend their antennae on demand. We hypothesized that hemolymph circulating through the antennae provides pressure that facilitates twisting and bending and provides a feedback control channel for tactile sensing in insects. To test this hypothesis, we conducted a thorough morphological and physiological analysis of antennae in three Clades of Blattodea. We studied morphology by evaluating the distinguishable features of the body and antenna, as well as the internal structure of the antennal lumen. Then, in a series of experiments on live cockroaches, we measured blood pressure along the antenna. This was …

Membrane Organization Of Rheb And Rhoa: Roles In Function And Allosteric Druggability, Chase M. Hutchins

Dissertations and Theses (Open Access)

Small GTPases of the Ras superfamily are membrane-bound molecular switches that regulate nearly all major cellular processes, and their dysregulation drives cancers, neurological disorders, and metabolic diseases. While anchored to cellular membranes, the catalytic domains of small GTPases undergo orientation dynamics, adopting distinct configurations that can occlude or expose effector-binding surfaces and modulate signaling output. These dynamics have been characterized in the Ras oncoproteins, but whether they extend across the superfamily and influence allosteric druggability has remained unknown.

In this dissertation, I address these questions through Rheb and RhoA, two small GTPases with complementary differences in subfamily lineage, membrane localization, …

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Mechanisms Of Bacterial Glucokinase Inactivation Through Site-Specific Lysine Modification And Chemical Inhibition, Joseph Robert Will Andrews

Graduate Theses and Dissertations

Glycolysis and related metabolic pathways are controlled by various post-translational modifications (PTMs) that affect enzyme activity and metabolic flow. In E. coli, glucokinase (GLK) sits at the crossroads of glycolysis and the pentose phosphate pathway and carries out the first committed step of glycolysis: ATP-dependent phosphorylation of glucose. While it's known that glucose binding causes GLK to close its domains, how phosphate binding, lysine modification, and small-molecule inhibitors regulate GLK's shape and function is still not fully understood. Here, I combine structural biochemistry and enzymology to figure out how phosphate binding, specific mutations, and chemical inhibitors affect E. coli GLK. …

A Novel Method Of Protein Purification Using Hedgehog Proteins As An Inducible, Self-Cleaving Tag, Antonia Kladias

Undergraduate Honors Theses

Because removing extraneous purification tag sequences from native proteins can be challenging and costly, there is demand for simple all-in-one techniques that directly furnish a tagless, functional protein-of-interest (POI). Current tagless purification systems are based on intein biochemistry; however, intein-based purification requires expensive, specialized resins and the POI often must be fused to the intein’s C-terminus. In this thesis, I present a novel approach for tagless POI purification in which the Drosophila melanogaster hedgehog protein catalytic domain (HhC) is repurposed as a small-molecule inducible, self-cleaving element dubbed Gtag. With Gtag, the POI is fused to the N-terminus of HhC/Gtag with …

Dried Water Treatment Residuals Might Be An Option To Reduce Soluble Reactive Phosphorus Release From Soils, Katie B. Mckay

Biological and Agricultural Engineering Undergraduate Honors Theses

Nonpoint source pollution from agricultural landscapes contributes to freshwater eutrophication, with legacy phosphorus (P) in soils potentially driving soluble reactive phosphorus (SRP) losses to surface waters. The objectives of this study were to evaluate SRP adsorption by dried water treatment residuals (WTRs) produced by Beaver Water District, quantify reductions in soil SRP release across increasing WTR application rates, and compare dried WTR performance to prior WTR studies.

Dried WTRs (~98% solids) were assessed using batch sorption experiments and soil core incubations. Phosphorus sorption was measured by mixing WTRs with CaCl₂ solutions containing increasing SRP concentrations and fitting results to …

Understanding The Role Of Toxs As A Bile Sensing Component Of The Toxrs Virulence Regulatory System In Vibrio Spp., Minje Kim

Dartmouth College Ph.D Dissertations

Pathogenic Vibrio bacteria, such as V. cholerae and V. parahaemolyticus, colonize in the human small intestine to cause severe gastrointestinal disease. During the infection, these bacteria encounter bile salts, antimicrobial cholesterol metabolites secreted into the intestine. Pathogenic Vibrio species have evolved to utilize bile salts as signals to regulate virulence. The signaling depends in part on ToxRS, a conserved co-component transmembrane transcription regulator. ToxRS consists of the transcription factor ToxR and its membrane-tethered binding partner ToxS. ToxS is required for ToxR stability and full transcriptional activity. Although bile salts are known to influence ToxRS-dependent virulence gene expression, the molecular …

Characterization Of Snrk1 Signaling In Rice Growth, Reproduction, And Stress Responses Using Phenotypic And Omics Analysis, Maria Clara Faria-Bates

Graduate Theses and Dissertations

SnRK1 is an evolutionarily conserved protein kinase belonging to the SNF1/AMPK family that is composed of a catalytic subunit (α) and two regulatory subunits (β and βγ), and it has a major role in adjusting growth in response to the energy status. SnRK1 phosphorylates and alters the activities of enzymes involved in metabolism and regulates gene expression by altering the activity of chromatin-remodeling enzymes or transcription factors. Rice contains three functional paralogs of SnRK1α: OsSnRK1αA (Os05g0530500), OsSnRK1αB (Os8g0484600), and OsSnRK1αC (Os03g0289100). Although SnRK1 is known to play a central role in plant growth and stress responses, the functional specialization of …

Sensing Rna’S Conformation With A Solid-State Nanopore Device At Various Ph And Temperature, Haopeng Li

Graduate Theses and Dissertations

This study uses solid-state nanopore technology to investigate the stability and dynamics of RNA molecules under thermal stress and pH fluctuations. Two distinct mRNA samples were analyzed: (1) heat shock protein (HSP)-encoding mRNA extracted from Sulfolobus solfataricus P2, a thermophilic archaeon inhabiting extreme environments such as geothermal sulfuric hot springs (pH < 4, temperature range: 65–90°C), and (2) total RNA extracted from White Leghorn chickens, which thrive under standard physiological conditions. ΦX174 virion single-stranded DNA (ssDNA) were included as a comparative reference. Nanopores, fabricated in silicon nitride membranes, were used to electrically characterize the structural properties of individual RNA molecules in solution, close to their native environments. The nanopore membrane separates two chambers containing salt buffer solution, where ionic current is the primary measurement parameter. When a voltage bias is applied across the membrane, ion flow and an ionic current can be measured. Charged RNA molecules driven translocation through the nanopore induces pore resistance changes, resulting in detectable current blockade events. Variations in these events provide insights into RNA secondary structure and conformational dynamics. By systematically altering pH and temperature, this study elucidates the effects of environmental stressors on RNA stability and structural integrity. The findings reveal distinct responses between thermophilic HSP-encoding mRNA and mesophilic RNA, underscoring the adaptive mechanisms of thermophilic RNA under extreme conditions. These results contribute to a better understanding of RNA behavior under stress and establish a foundation for future applications in RNA-based diagnostics and biotechnology development.

Nonenzymatic Glycation Of Human Serum Albumin Affects Its Structure, Properties, And Binding Interactions With Silver Nanoparticles, Monica Fairchild, Megan Kirk, Collin Kray

Celebrating Scholarship and Creativity Day (2018-)

Most nanoparticles (1-100 nm), upon contact with proteins, form a “protein corona” which can alter the structure and function of proteins. Human serum albumin (HSA) is the most abundant protein in blood plasma and acts as a major transport protein for numerous endogenous and exogenous compounds. In healthy individuals, 1-10% HSA is found in a glycated state, but significantly higher levels of glycated HSA (30% or more) are found in Diabetic individuals. This project investigates the effects of glycation on the structure, enzymatic activity, and antioxidant capacity of HSA and its binding interactions with silver nanoparticles (AgNPs) using a variety …

Beyond The Brain: Environmental Forces Driving Α-Synuclein Misfolding And Toxic Aggregation In Parkinson's Disease, Emily Mccarthy

Celebrating Scholarship and Creativity Day (2018-)

Parkinson's disease (PD) is an advanced neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and the proliferation of protein aggregates within the brain. This capstone thesis investigates the unique biochemical environment of the gastrointestinal tract and whether it contributes to the formation of distinctive α-Synuclein (αSyn) aggregates affecting PD. Key promoters of αSyn aggregation include genetic mutations, oxidative stress, post-translational modifications, interactions with metal ions, and dopamine (DA) oxidation. These factors result in diverse structures such as oligomers, protofibrils, and fibrils, which result in unique functional outcomes, with oligomeric conformations leading to the highest level of neuronal toxicity. Evidence …

Elucidating The Role Of The Gastrointestinal Microbiome And Diet In Dopamine Release In Relation To Attention-Deficit/Hyperactivity Disorder., Meaghan Mcdonald

Celebrating Scholarship and Creativity Day (2018-)

Currently affecting 340-580 million people worldwide, ADHD is a neurodevelopmental disorder that affects how the brain controls attention, behaviour and impulses often beginning in childhood and continuing into adulthood. ADHD is known to be associated with monoamine neurotransmitters including dopamine. This work aims to uncover the ways in which metabolism of monoamine precursors in the gastrointestinal microbiome influences dopamine release in the brain. Previous studies have indicated that children with ADHD display distinct gut bacteria profiles with unique microbiota species that result in the disruption of monoamine precursor pathways of phenylalanine and tyrosine metabolism. Emphasis on our western diet and …

The Impact Of Hybrid Insulin Peptides On The Two-Phase Decline Of C-Peptide In Type 1 Diabetes, Ashley Mehl

Celebrating Scholarship and Creativity Day (2018-)

This research aims to determine how the formation of hybrid insulin peptides (HIPs) contributes to the two-phase decline of C-peptide production in type 1 diabetes (T1D). C-peptide is used to determine the level of insulin production within human pancreatic beta-cells because it is secreted in equimolar amounts with mature insulin peptide. The two-phase decline is characterized by an initial rapid and exponential loss of beta-cell function, followed by a prolonged plateau phase of residual insulin secretion. During this plateau phase, residual beta-cells continue to generate HIPs through both enzymatic transpeptidation and spontaneous formation via anhydride intermediates. These processes are problematic …

Cleft Palate And The Coordination Of Wnt Signaling And Pax9 In Murine Palatogenesis, Landon Wyatt

Honors Theses

Cleft palate is a common craniofacial birth defect that arises when the molecular and morphogenetic events guiding secondary palate formation lose coordination during a narrow developmental window. In mice, successful palatogenesis requires the paired palatal shelves to grow vertically, elevate above the tongue, and fuse at the midline; disruption of any of these steps can result in clefting. Two important regulators of this process are canonical Wnt signaling and the transcription factor Pax9, both of which contribute to normal palatal mesenchymal growth and patterning during early development. This paper first examines whether altered Dkk1/Wnt signaling contributes to the Pax9-null palate …