Molecular Biology Commons^™

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …

Characterizing The Human Metapneumovirus Matrix Protein And Its Role In Infection, Chase J. Heim

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) causes severe respiratory tract infections in all cohorts, but especially in vulnerable groups such as children, older adults, and the immunocompromised. The matrix (M) protein of HMPV, like the M proteins of other members of the Mononegavirales order, is involved in virus assembly and budding. However, other functions of the HMPV M protein have yet to be elucidated. To investigate these various functions of the M protein, we used a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) antisense agent designed to block translation of the M gene to reduce M expression during infection. Treatment with varying concentrations of an …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Development Of A Split Deoxyribozyme-Based Assay For Detecting Hepatitis B Virus, Dalila Zovko

Honors Undergraduate Theses

Rapid, accessible nucleic acid-based detection methods are needed for hepatitis B virus (HBV). A split deoxyribozyme assay was developed for sequence-specific fluorescence detection. The assay was evaluated using synthetic target and plasmid-derived material. The assay showed target-dependent fluorescence and low-concentration linear range with a LOD of 1.9 nM. The assay supports detection and semi-quantification of HBV genetic material as shown using plasmid-derived transcript samples from HBV genotypes B, C, and D. The selected target corresponded to nt 363–406 of the HBV genome and was chosen based on sequence alignment showing conservation across most genotypes. Genotype-specific detection remains a future application …

Dna Half-Adder Based Calculator Driven By 4j Molecular Switches, Andrea Gissele Canizalez Covaleda

Honors Undergraduate Theses

DNA nanostructures have computing functions due to the predictable base pairing of nucleic acids (Watson–Crick). This property allows the programming of DNA circuits that integrate DNA logic gates capable of recognizing oligonucleotides. This molecular device offers the advantages of biocompatibility and potential applications in personalized medicine for diagnosis and therapies.

Our lab has developed DNA logic gates formed by the connection of YES strands via DNA four-way junctions (4J), which can function as molecular switches to develop a DNA-based calculator. Our DNA half-adder calculator nanostructure is designed to recognize up to three combinations of DNA inputs using three DNA strands …

Antiestrogens As Bone Protective Therapeutics For Estrogen Receptor-Positive Breast Cancer In The Presence Of Osteoporosis, Faith E. Parker, Emily K. Zboril, David C. Boyd, Rachel Myrick, J. Chuck Harrell

Undergraduate Research Posters

Breast cancer (BC) is one of the most significant causes of mortality among women and the second leading cause of cancer death in women. The estrogen receptor (ER) is a key oncogenic driver in the majority of breast cancer. ER+ BC is the most common molecular subtype of BC. Management of ER+ breast cancer varies depending on menopausal status. For premenopausal women, the goal is to suppress estradiol production from the ovaries with surgical oophorectomy and/or aromatase inhibitors. In postmenopausal women, endocrine therapy (ET) serves to suppress estradiol production from sources other than the ovaries. During the menopausal transition, estradiol …

Patterns Of Ovarian And Gonadotropin Hormones In Emerging Adult Oral Contraceptive Users, Summer Mcormond

Undergraduate Research Posters

Oral contraceptives (OCs) are often initiated during adolescence and emerging adulthood, a period of continued maturation of the hypothalamic–pituitary–gonadal (HPG) axis. Because hormonal exposure during this window may shape emotional, biological, and reproductive outcomes, it is important to understand the specific formulations young women take and the hormonal profiles these formulations produce. This study characterizes OC formulation features and measured hormone levels in young adult OC users (n = 30).

Ethinyl estradiol (EE) doses ranged from 0.01–0.035 mg (mean = 0.022 mg), with 70% using ≤0.02 mg. Pill regimens included 21/7 packs (83%), 24/4 packs (10%), and 84/7 regimens (3%). …

Psr Impacts Chromatin Condensation During Spermatogenesis In Nasonia Vitripennis, Jacqueline R. Solomon

CMC Senior Theses

Paternal Sex Ratio (PSR) is a supernumerary, selfish B chromosome found in the jewel wasp (Nasonia vitripennis). PSR is transmitted strictly paternally to progeny, and when present, it causes paternal genome elimination (PGE) just after fertilization. Due to the haplo-diploid reproduction of N. vitripennis, this PGE event results in all-male broods of progeny, ~90% of which carry and transmit PSR. Thus, PGE is beneficial for PSR’s transmission.  A previous study showed that PSR induces PGE by expressing a gene called haploidizer during spermatogenesis. Although how haploidizer functions in PGE is unknown, this finding suggests two basic models: that (i) the …

The Geminivirus Al2 Protein Interacts With Host Proteins Involved In The Plant Antiviral Response, Pheobean Atieno Odongo

Graduate Research Theses & Dissertations

Geminiviruses are economically important plant DNA viruses infecting a broad range of plant species and causing devastating crop diseases, resulting in up to 100% crop loss. As a result of these heavy losses on food and cash crops, these viruses represent a new threat to global food security and sustainability. In this research, I use Tomato golden mosaic virus (TGMV) to study host-virus relationships with an overall goal of developing sustainable and eco-friendly crop resistance. TGMV belongs to the Geminivirus subgroup, Begomovirus, that is characterized by a split genome consisting of two single-stranded circular DNAs. The TGMV genome encodes proteins …

The Biosynthesis Of The Natural Product N-Nitroglycine, Gabriel Padilla

Graduate Studies Theses and Dissertations 2026

N-Nitroglycine (NNG) is a nitramine [R(R′)N–NO2; R′=H or alkyl] natural product (NP) produced by certain actinomycetes, such as Streptomyces noursei. At the beginning of this project, the biosynthesis of this NP was unknown. The goal was to determine how NNG and its nitramine moiety are enzymatically formed. This could lead to the discovery of novel nitramine NPs with diverse applications as well as alternative/green synthesis of nitramine explosives. This work begins by examining diverse biochemical N–N bond formation strategies. Nitrogen cycle enzymes, nitration of NPs, kutzneride biosynthesis, the aspartate/nitrosuccinate superfamily, hydrazinoacetic acid (HAA) biosynthesis, and streptozocin biosynthesis are among the …

Evaluating Novel Targeted Combination Therapies For Gastrointestinal Cancers, Joseph A. Goode

Graduate Studies Theses and Dissertations 2026

Gastrointestinal (GI) cancers remain among the leading causes of cancer-related mortality worldwide, with therapeutic resistance continuing to limit the effectiveness of current treatments. Three complementary studies were conducted to identify therapeutic vulnerabilities and evaluate novel combination strategies in pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC).  First, dual inhibition of fibroblast growth factor receptor 4 (FGFR4) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling was investigated in PDAC models. A combination of targeted drug treatments reduced viability, clonogenic survival, migration, and suppressed signaling pathways involved in translational control. This supported a functional interaction between FGFR4 and PI3K-mTOR co-activation in …

Role Of The Osaa Transcription Factor Gene In Development, Secondary Metabolism And Virulence In The Mycotoxigenic Fungus Aspergillus Flavus, Farzana Ehetasum Hossain

Graduate Research Theses & Dissertations

Aspergillus flavus colonizes oil-seed crops, contaminating them with aflatoxins; highly carcinogenic mycotoxins that cause severe health and economic losses. Genetic studies may reveal new targets for effective control strategies. Here, we characterized a putative WOPR transcription factor gene, osaA, in A. flavus. Our results revealed that osaA regulates conidiation and sclerotial formation. Importantly, deletion of osaA reduces aflatoxin B1 production, while, unexpectedly, transcriptome analysis indicated upregulation of aflatoxin biosynthetic genes, suggesting post-transcriptional or cofactor-mediated regulation. Cyclopiazonic acid production also decreased in the absence of osaA. In addition, the osaA mutant exhibited upregulation of genes in the imizoquin and aspirochlorine clusters. …

The Importance Of The Proline Residue In The Ldiapa Motif Of Cholera Toxin, Akash Bharathan

Honors Undergraduate Theses

Cholera is currently on its seventh global pandemic, disproportionately affecting developing countries. Vibrio cholerae, the bacterial etiologic agent, is able to cause infection by adhering to intestinal epithelial cells and secreting cholera toxin (CT), an AB-type exotoxin that dysregulates signaling pathways. Previous research by the Teter lab has shown that Hsp90, a host cytosolic chaperone, is required for CT to enter the cytosol where it produces toxic effects. Hsp90 binds to CT at two specific motifs, RPPDEI and LDIAPA. The prolines in the RPPDEI motif are essential for binding, but the proline in the LDIAPA has yet to be …

Fluorescent Protein Imaging Approaches Uncover Dynamic Subcellular Distribution Of Core Clock Proteins In Neurospora Crassa, Ziyan Wang

Dartmouth College Ph.D Dissertations

Circadian clocks are endogenous self-sustained timekeeping systems that allow organisms to anticipate and adapt to daily environmental cycles. Found in diverse forms of life, these molecular clocks regulate the expression of ~ 40% of the genome in animals, fungi, and plants. In animals and fungi, circadian oscillators are built on transcription-translation feedback loops (TTFLs), in which positive regulators drive the expression of negative regulators which, once synthesized and imported into the nucleus, inhibit their own activators. This precisely regulated negative feedback incorporates multiple steps of delays that are essential for generating ~24-hour rhythms. Through these mechanisms, circadian clocks temporally coordinate …

Analysis Of Alternative Oxidase In Non-Angiosperm Plants, Anissa M. Francis

Theses and Dissertations (Comprehensive)

Alternative oxidase (AOX) is a mitochondrial terminal oxidase that provides an alternative pathway for electron transport, allowing plants to maintain respiratory flexibility under environmental stress conditions. While AOX has been extensively studied in angiosperms (flowering plants), little is known about its distribution and conservation in non-angiosperms. Based on gaps identified in the literature, this thesis investigated the distribution of AOX across non-angiosperm plant lineages. Although AOX is present in many green algae and is therefore considered to be an ancient protein that originated before the existence of non-angiosperm plants, it remains unclear whether the protein is uniformly distributed across these …

Self-Assembling Rna Nanostructures Are Highly Sensitive To Environmental Conditions, Jordan Aposhian, Surya Pratap S. Deopa, Scott Horowitz, Joseph D. Yesselman

Chemistry and Biochemistry: Faculty Scholarship

Recent developments in RNA nanotechnology have led to an increase in the design of specific, higher-order RNA structures, which will ultimately be used in drug delivery and immunomodulation applications. As researchers create RNA nanostructures with the intention of making them a standard tool in molecular biologists' toolkits, further investigation is required into the robustness of RNA designs. Primarily, in what different molecular contexts are the designed and intended nanostructures stable? In this work, we show that RNA nanostructure self-assembly is highly sensitive to environmental conditions by using second-order right-angle light scattering. While a test RNA hexagonal grid nanostructure forms correctly …

Development Of Self-Assembled Polymeric Polyplexes For Microrna Delivery: Toward Treatment Of Alcohol-Associated Liver Disease, Marjina Akter Kalpana

Theses & Dissertations

Self-assembled polymeric polyplexes have the potential to serve as an RNA interference (RNAi) delivery platform for the combined inhibition of CXCR4 and miR-155 in the treatment of alcohol-associated liver disease (AALD). A central challenge in RNA delivery is balancing the extracellular stability of polyplexes, cellular uptake, and intracellular release of RNA cargo. We developed polymeric polyplexes using the CXCR4-antagonist polymer PAMD, designed to target CXCR4 on activated hepatic stellate cells (HSCs) and deliver therapeutic miRNA to activated Kupffer cells (KCs) in fibrotic liver. We improved the polyplexes by cholesterol modification of PAMD and by PEGylation of PAMD-Ch. The cholesterol modification …

Evaluating Bmx-001 As A Selective Radioprotector For Healthy Tissue In Pelvic Cancers, Molly Myers

Theses & Dissertations

Pelvic cancers, including rectal, anal, and prostate cancer, are relatively survivable cancers with high five-year survival rates, partially due to the addition of radiation to treatment regimens. Radiation confers excellent tumor control, but also causes damage to surrounding tissue, resulting in both short-term and long-term side effects. In a patient population that is surviving longer after treatment, limiting the impact of side effects is instrumental to improving patient quality of life. Radiation-induced ROS is instrumental in causing these side effects and provides a unique opportunity to protect healthy tissue from damage while sensitizing cancer tissue to treatment, as cancer cells …

Investigating The Role And Mechanism Of Faecalibacterium Prausnitzii In Fatty Acid Metabolism And Obesity Using The Drosophila Melanogaster Model, Jackson Head, Whitley Whitehead

Student Scholar Symposium

The obesity epidemic has increased to enormous numbers with 890 million adults being classified as obese (BMI≥30). Obesity is of extreme concern as it is a comorbidity to coronary heart disease, type-2 diabetes, and cancer. Although obesity has classically been attributed to genetics and lifestyle, there is a growing interest in other factors, including the gut microbiome. Germ-free mice are resistant to weight gain even when placed on a high-calorie diet, establishing that metabolites produced by gut microbiota can dramatically inhibit metabolism. Here, we use Faecalibacterium prausnitzii, which has been previously shown to be reduced in obese individuals; however, …

Indole Improves Outcomes Of Cronobacter Sakazakii Infection In C. Elegans Through Ahr-1, Cayden Durrough

Student Scholar Symposium

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease primarily affecting premature infants. Toll-like receptor 4 (TLR4)-mediated epithelial damage allows microbial translocation, triggering inflammation that can lead to sepsis and death. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, and AhR ligands have been shown to prevent NEC in a mouse model. Indole, an AhR ligand, has been reported to extend the healthspan of C. elegans, and we have shown previously it mitigates poor outcomes in wild-type worms infected with Cronobacter sakazakii (Cs), a bacterial pathogen linked to NEC. We hypothesized that C. elegans must express ahr-1, the ortholog …