Molecular Biology Commons^™

Bioinformatic Resolution Of Candidate Stress-Response Homologs In Cryptosporidium Parvum: P53-Family Vs Sestrin Identity, Freeman Tobechukwu Ezeala Mr.

Biochemistry and Molecular Biology

Cryptosporidium parvum is an apicomplexan protozoan of major public-health importance, but accurate genome annotation in this organism remains difficult because of its compact genome, deep protein divergence, and the presence of compositionally biased or low-complexity regions that can mislead similarity-based analysis.

In this thesis, I examined one such annotation problem involving a conserved Cryptosporidium stress-response candidate protein, CPATCC_0028580_t1 (833 aa). The central question was whether this protein is better interpreted as a member of the p53 family, based on similarity to p53-like DNA-binding domains (PF00870), or as a member of the Sestrin family associated with the PA26 domain.

I explored …

The Universe Under A Microscope, Claire Chabot

Caravel Undergraduate Research Journal

No abstract provided.

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. …

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 …

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 …

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 …

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 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 …

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 …

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 …

Assessing The Use Of Exon-Skipping Morpholino Antisense Oligonucleotides Targeting The Different Sumo Paralogs As Enhancers Of The Antitumor Activity Of Chemotherapeutic Agents, Andrea Teresa Garcia-Morin

Open Access Theses & Dissertations

Post-translational modifications (PTMs) are critical regulators of protein function, stability, and localization, with SUMOylation emerging as a key modulator of cellular stress response and survival in cancer. Non-small cell lung cancer (NSCLC) is characterized by heightened dependence on SUMOylation to sustain pro-survival signaling, DNA repair, and resistance to chemotherapy. This dissertation investigates a novel chemosensitization strategy based on the splice-switching of SUMO transcripts in NSCLC cells using exon-skipping morpholinos (ESMs), which redirect splicing toward non-conjugatable SUMO alpha isoforms, thereby reducing global SUMOylation. We hypothesized that decreasing global SUMOylation through forced alternative splicing of SUMO transcripts would impair the stress-protective functions …

Novel Roles Of G-Beta-Gamma Signaling In Microtubule Dynamics And Neurodegeneration, Diana I. Olivas

Open Access Theses & Dissertations

Neurodegenerative disorders (NDDs), including Alzheimer's disease (AD), are characterized by progressive neuronal dysfunction, cytoskeletal disruption, and cognitive decline. Although Tau hyperphosphorylation and neurofibrillary tangle (NFT) formation are classical hallmarks of AD, emerging evidence suggests that microtubule (MT) dysfunction may precede and occur independently of Tau pathology. Understanding upstream regulators of MT dynamics is therefore critical for elucidating early mechanisms of neurodegeneration. Previous work from our laboratory demonstrated that G protein βγ (Gβγ) subunits directly interact with tubulin and promote MT assembly. However, the mechanism of Gβγ signaling in neuronal cytoskeletal stability and neurodegeneration remained poorly understood. The present study investigated …

Drug Repurposing Against Giardia Targeting Lipid Rafts, Extracellular Vesicles, And Sphingolipid Synthesis, Breanna Chantal Pence

Open Access Theses & Dissertations

Giardia lamblia is a protozoan parasite responsible for the intestinal disease giardiasis worldwide. Giardia is one of the major intestinal parasites in the world, with over 500,000 new cases annually. Symptoms of giardiasis include diarrhea, abdominal pain, and nausea. Children are particularly vulnerable to giardiasis, with cases of malnutrition, stunted growth, and cognitive impairment in countries where the disease is endemic. Giardia consists of two morphologic forms: an infective cyst which transmits the disease and a motile trophozoite which attaches to the epithelium of the small intestine during infection. Metronidazole is a common treatment for giardiasis, but cases of toxicity …

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 …

Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith

Senior Honors Theses

Type 2 diabetes mellitus (T2D) is one of the leading causes of morbidity and mortality in the United States, with approximately 25% of healthcare expenditures directed toward its management and associated metabolic complications. In response to the urgent need for novel therapeutic strategies, recent research has focused on bioactive compounds derived from dietary sources. In light of that, we identified the plant lignan matairesinol (MA) and its gut-derived metabolite, enterolactone (ENL), as agents capable of enhancing glucose uptake in 3T3-L1 differentiated adipocytes. These results suggest that enterolactone may represent a promising dietary supplement for improving glycemic control in patients with …

The Pam-1 Aminopeptidase Does Not Protect Against Ptl-1 Mediated Neurodegeneration In C. Elegans., Ethan E. Schuff

Honors College Theses

Debilitating neurodegenerative conditions are increasingly prevalent in our aging population, yet treatment options remain limited. Though neurodegenerative diseases vary in pathophysiology and clinical manifestations, these diseases are related to one another in that many involve misfolded proteins. Tau is a member of the microtubule-stabilizing MAPT/MAP2/MAP4 family, and misfolded tau proteins form the neurotoxic aggregates called neurofibrillary tangles (NFTs) found in the brains of patients with Alzheimer's disease and other neurodegenerative diseases. Designing a study to elucidate the neurotoxic role of tau is difficult because other MAPs may have compensatory mechanisms which confound study data. Caenorhabditis elegans (C. elegans) …

Pepper Spray Exposure And The Effect On Dna Profiling Of Blood, Brandon Schmakel

Honors Projects

Pepper spray is a common self defense tool used in both law enforcement and civilian settings, with the goal of incapacitating the sprayed individual. In real casework where pepper spray was used, a red-brown stain which tested positive presumptively for blood provided no DNA profile after further testing six months later. A previous graduate student, Emma Crawn, attempted to emulate these casework conditions and instead achieved a DNA profile with slight indications of inhibition or degradation. Further analysis of active pepper spray ingredients such as Oleoresin Capsicum (OC) and Chloroacetophenone (CN) reveals that there are observed reactions, such as oxidation, …