Life Sciences Commons^™

A Screen Of Fda-Approved Drugs Identifies Inhibitors Of Protein Tyrosine Phosphatase 4a3 (Ptp4a3 Or Prl-3), Dylan R. Rivas, Mark Vincent C. Dela Cerna, Caroline N. Smith, Shilpa Sampathi, Blaine G. Patty, Donghan Lee, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells ...

A Tissue Specific Transcriptomic, Proteomic And Phospho-Proteomic Atlas Of The Translational Machinery Of Arabidopsis Thaliana, Abdullah Salim

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Gene expression encompasses the flow of genetic information from DNA to mRNA (transcription) and from mRNA to protein (translation) along with the regulatory mechanisms underlying these processes. Omics technologies offer a powerful toolset with which to study gene expression at each of these stages. A recently published dataset integrating transcriptomic, proteomic and phospho-proteomic measurements from 30 Arabidopsis thaliana tissues provides a unique resource to explore gene expression.¹ The translational machinery (the ribosome, and its initiation, elongation, and termination factors) are a core component in gene expression. Defects in translation can be lethal or lead to major developmental defects and ...

Project Alien, Rebecca Mccallin, Madelyn Hoying, Alex Evans, Matthew Nestler, Karli Rae Sutton, Garett Craig, Lucia Secaia Del Cid, Alexander Guy, Rachel Fernandez, Amanda Trusiak, Paige Aley, Ingabire Gakwerere, Nina Dorfner, Maria Mosbacher, Mary Flavin, Selvin Hernandez, Audrey Steen, Benjamin Kazimer

Undergraduate Research and Scholarship Symposium

Project ALIEN is a comprehensive plan to send humans to Mars to look for life on the Martian surface while exploring the viability and adaptability of terrestrial microbes in Martian atmospheric conditions. ALIEN will use a ballistic capture trajectory to get to Mars and stay in aerostationary orbit for a 30-day surface mission, during which two surface crewmembers will perform a variety of experiments to achieve the mission’s goals of Martian microbial discovery within brines of the Gale Crater and terrestrial microbe adaptability and viability to Martian conditions. Experimentation is based on the presumption that Martian microbes are metabolically ...

Designing A Reactive Warhead To Bind And Inhibit Pseudomonas Aeruginosa’S Periplasmic Protein, Inhibitor Of Vertebrate Lysozyme, Leah Greinke

Master of Science in Chemical Sciences Theses

Pseudomonas aeruginosa is a Gram-negative bacterium commonly found throughout the environment. It is a significant cause of disease and mortality in immunodeficient patients such as those suffering from cystic fibrosis (CF). Due to the emerging antibiotic resistance of P. aeruginosa, it is becoming increasingly more challenging to treat an infection by traditional means. Further complicating treatment, P. aeruginosa secretes a protein known as Inhibitor of Vertebrate Lysozyme (PaIVY) that binds to and inhibits C-type lysozyme, thus preventing the degradation of the bacterium. A reactive chemical warhead was synthesized from a rhenium(I) tricarbonyl derivative inorder to bind to and irreversibly ...

Search For Palladin, An Actin-Associated Protein, In Pig Retinal Pigmented Epithelium And Its Role In Epithelial-Mesenchymal Transition, Katrina Powell

Undergraduate Theses

This study investigates the expression of Palladin, a phosphoprotein product of the PALLD gene, in the retinal pigmented epithelium (RPE). Palladin is an actin cross-linking protein and plays a role in cell adhesion and motility. Published reports have demonstrated that a down regulation of Palladin in colon cancer cells results in a reorganization of the actin cytoskeleton, causing the cells to lose their typical shape, become proliferative and migratory. This process is otherwise known as epithelial-mesenchymal transition (EMT). A similar EMT phenomenon is observed when the RPE is exposed to the vitreous humor in patients with proliferative vitreoretinopathy (PVR). In ...

Integrative Computational Approach Identifies Drug Targets In Cd4+ T-Cell-Mediated Immune Disorders, Bhanwar L. Puniya, Rada Amin, Bailee Lichter, Robert Moore, Alex Ciurej, Sydney J. Bennett, Ab Rauf Shah, Matteo Barberis, Tomáš Helikar

Biochemistry -- Faculty Publications

CD4⁺ T cells provide adaptive immunity against pathogens and abnormal cells, and they are also associated with various immunerelated diseases. CD4⁺ T cells’ metabolism is dysregulated in these pathologies and represents an opportunity for drug discovery and development. Genome-scale metabolic modeling offers an opportunity to accelerate drug discovery by providing high-quality information about possible target space in the context of a modeled disease. Here, we develop genome-scale models of naïve, Th1, Th2, and Th17 CD4⁺ T-cell subtypes to map metabolic perturbations in rheumatoid arthritis, multiple sclerosis, and primary biliary cholangitis. We subjected these models to in silico simulations for drug ...

Fundamental Causes Of Racial And Ethnic Covid-19-Related Health Disparities, Hana Neutz

Student Scholar Symposium Abstracts and Posters

Underserved low-income communities of color in the U.S. have endured an unequal burden of COVID-19 morbidity and mortality. This pattern of pandemic-related health disparities has been pervasive throughout history. However, no known studies have simultaneously examined social and biological factors that contribute to these concerning health disparities. Therefore, this paper aims to bridge the gap by employing a scoping literature review of (1) the deleterious impacts of systemic racism on COVID-19-related outcomes; and (2) the cellular and molecular mechanisms connecting COVID-19 and hypertension (a comorbidity known to exacerbate COVID-19 severity). My findings indicate that systemic racism manifests in inequitable ...

Effects Of Crowding Agents On I-Motif Dna, Hayden Brines

Honors Theses

Deoxyribonucleic acid (DNA) is a well-known double stranded, helical, biological molecule. In addition to its more commonly known structure, DNA can also form more complicated structures like G-quadruplexes and i-motifs (iM). The iMs are formed by cytosine rich DNA and are a four stranded structure that is typically looped around itself. The iM formation is typically pH-dependent and is favored in more acidic conditions; the pKa value is approximately 6.5. This pKa value allows for potential in vivo formation, since the cells have a pH of approximately 7.3. Due to this, iMs are thought to be powerful, innovative ...

Validation Of Anti-Oxidative Stress Genes From Genome-Wide Screening Of Escherichia Coli, Carson Ercanbrack

Chemistry & Biochemistry Undergraduate Honors Theses

The primary purpose of this project is to evaluate the genes that play a role in the oxidative stress response in Escherichia coli. In doing so, the entire genome of E. coli was subject to throughput in which individual genes were determined to have a role in the bacteria’s oxidative stress response. Moreover, this project focused on the validation of the genes that were able to pass the initial throughput stage. The genes were subject to two forms of validation. In the first validation technique, candidate genes were overexpressed and minimum inhibitory concentrations of hypochlorous acid were taken. Following ...

The Effect Of The Apolipoprotein A1 (Apoa1): The Stability And Folding In Potassium Chloride Environment, Alexandra Paladian

Honors Theses

Healthy levels of potassium chloride (KCl) can significantly affect the workings of the cholesterol level of the human body and how they pertain to an individual person. The search for a better salt additive for the human diet can provide a better option for people who experience high cholesterol levels and heart disease. The study focuses on the experimental design of the Molecular Dynamic (MD) simulation of the Apolipoprotein A1 (APOA1) in the potassium ion solution environment to determine the stability and folding of the protein. The study also compares its data to the previous experimental design of chloride ions ...

Molecular Dynamic Simulation Of The Complex Folding Patterns Of Apolipoprotein A1 In Various Concentrations Of Potassium Chloride, Hannah Holmberg

Honors Theses

Apopliprotein or ApoA-1 is a complex lipoprotein that functions in the removal of cholesterol from the blood, removing cholesterol from the area around white blood cells and promoting the excretion of lipids through the lymphatic system. Previous research has found that ApoA-1 shows both folded and unfolded conformations depending on the concentration of NaCl in solution in the water around it. The protein was studied using molecular dynamics simulations. Once this state of equilibrium was reached, various structural properties of the protein were measured including the radius of gyration and the radial distribution function. The goal of the project was ...

Studies Of The Dutpase Of The Western Corn Rootworm, Carlos Riera-Ruiz

Dissertations and Theses in Biological Sciences

The western corn rootworm (WCR), Diabrotica virgifera virgifera, is a major corn pest in the United States and Europe. WCR has developed resistance to multiple management strategies, including Cry proteins. Even though the biology and ecology have been thoroughly studied in WCR, their genome and molecular mechanisms are understudied. This work focuses on the ubiquitous enzyme deoxyuridine triphosphatase (dUTPase) encoded by the DUT gene. dUTPase hydrolyzes dUTP into dUMP and pyrophosphate. It contributes to genome stability by keeping the uracil-to-thymine ratio at a certain level. In WCR, two dUTPase isoforms were predicted using transcriptome analyses. These two potential isoforms shared ...

Using Crispr-Cas9 To Characterize The Role Of Gli-Similar 3 (Glis3) In Insulin Regulation, Pancreatic Development, And Type 2 Diabetes, Lilyanne Grieve

Honors College Theses

The prevalence of type 2 diabetes continues to rise nationally and internationally, impacting millions of people worldwide. Type 2 diabetes results from insulin resistance leading to chronic hyperinsulinemia and dysfunction of the insulin producing β cells of the pancreas. While environmental factors can influence the development of type 2 diabetes, research has shown genetics are also involved. Gli-similar 3 (Glis3), a Krüppel-like zinc finger transcription factor, has been identified as a novel regulator of insulin transcription. Evidence has shown that loss-of-function Glis3 mutations decrease insulin expression, implicating Glis3 in the development of type 2 diabetes. However, the distinct role Glis3 ...

Analyzing The Effects Of E-Hook Peptides On Kinesin-1, Ashton Ward Murrah, Baylee Hope Howard

Honors Theses

Cancer is the second leading cause of death in the United States. Cancerous growth is a result of oncogenes, or mutated genes that increase the rate of cell division in an uncontrolled manner. Cell division, which consists of mitosis and cytokinesis phases, is dependent upon the active movement of kinesin motor proteins along microtubules to rearrange the cytoskeleton for equitable distribution of genetic material to daughter cells. As kinesins are vital to this process, if we could prevent kinesin from binding to the microtubules, cell division would cease.

The goal of this study is to develop a method to prevent ...

Sharing Raw Data From Bacterial Genomes For Collaborative Research On The Amped Server At Uri, Deborah Adenekan

Senior Honors Projects

No abstract provided.

Analyzing The Impacts Of Loss Of The Fanca Protein On Chromatin State, Mileena Nguyen

Senior Honors Projects

No abstract provided.

Nutritional Data And Corresponding Performance Impacts Of Uri Student-Athletes, Abigael Fenbert

Senior Honors Projects

This research project investigates the diets of various sport athletes at the University of Rhode Island. The question that this project aims to answer is if our athletes are meeting recommended daily values nutritionally, and if not, why? Research continues to grow regarding how performance implications are tied to varying nutritional disparities for athletes. Various studies show malnourishment leads to performance decline, increased injury risk, and improper recovery. This is influenced by factors such as deficits in caloric intake, macronutrient and micronutrient availability, and dehydration. For college athletes, a lack of food availability and nutritional knowledge leaves them especially predisposed ...

Investigations Of Substrate Reduction By Nitrogenase: Light Powered Substrate Reduction By A Cds:Femoco System And Understanding Dinitrogen Inhibition Of Electron Transfer, Hayden Kallas

All Graduate Theses and Dissertations

Nitrogen fixation is a key step of the nitrogen cycle which makes biologically inert N₂ gas available for organisms to use in the form of ammonia. Nitrogen fixing microorganisms all contain the same enzyme called nitrogenase which catalyzes the six electron transfers to N₂ required for conversion into ammonia. Nitrogenase is a two-component enzyme that contains a cofactor composed of iron and sulfur as well as heavier metals whose identity can be molybdenum, vanadium, or an additional iron atom depending on the variant. The two components of nitrogenase are the MFe protein and the Fe protein. The Fe ...

Finding The Balance​ The Effects Of Α-Cyclodextrin, 2-Hydroxypropyl-Β-Cyclodextrin, And Cholesterol Bacteroides Vulgatus And Clostridium Bolteae​, Bethany Weaver

Honors Program Projects

Atherosclerosis is a cardiovascular disease that is characterized by the hardening of arteries through the formation of cholesterol plaques. Cyclodextrins could potentially treat atherosclerosis by shrinking plaques. These cyclic oligosaccharides can make complexes with cholesterol but have also shown toxic side effects. This study looked for potential negative effects of cyclodextrins and cholesterol on gut bacteria. It was hypothesized that Bacteroides vulgatus will have decreased growth when grown in broth with cholesterol. In contrast, Clostridium bolteae will have decreased growth when grown in broth with cyclodextrins. Due to the fact that these bacteria are anaerobic, Clostridium bolteae and Bacteroides vulgatus ...

Proteomic Analysis Of Mycobacteriophage Crimd, William Moeller

Undergraduate Honors Theses

Bacteriophages represent a large portion of the biomatter on our planet, and many of them have yet to be fully characterized. Here we discuss the proteomic analysis of a particular Bacteriophage, Mycobacteriophage CrimD. This phage was discovered on the Campus of William & Mary and has had its genome characterized. We took the next logical step of proteomic analysis.

In our analyses we made use high pressure liquid chromatography paired with linear ion trap mass spectrometry to analyze the proteome of CrimD at specific time points after the infection of its host, Mycobacterium smegmatis. Additionally, we used nanospray ionization with in-house ...

Effects Of Environmentally Relevant Concentrations Of 4-Methyl-1- Cyclohexanemethanol (Mchm) On General Esterase And Glutathione-S-Transferase Activity In Fathead Minnows (Pimephales Promela), Emily De Wind

Research in Biology

Abstract

In 2014, several thousand gallons of coal-processing chemicals, which included 4-methyl-1- cyclohexanemethanol (MCHM), spilled into the Elk River in West Virginia. The location of this spill in West Virginia’s chemical valley is historically significant in defining the exploitations of people residing in this area. The concentration of crude MCHM in the river was approximated at 0.15 µg/L. Although some initial studies did consider the effects of MCHM exposure on humans, little attention has been given to aquatic wildlife. In this project, I will expose fathead minnows, Pimephales promelas, an environmentally relevant species, to concentrations of MCHM ...

Design, Simulation And Testing Of Biomimetic Directional Acoustic Sensors, Brendan Francis

Thinking Matters Symposium

The Ormia ochracea, a species of parasitic fly, has become the focal point in sound localization research because of its finely tuned hearing abilities. The female of this species uses its super highly directional hearing to pinpoint the call of a host cricket, with hypersensitivity of frequency and phase difference, to reach and dispose of its eggs on the host. The goal of this study was to further the research of a previous Project in Professor Guvench’s group which implemented MEMS (Micro Electro-Mechanical System) technology on a chip to replicate these abilities. In this iteration, however, some commercially available ...

Finite Element Analysis Of Impact Resistant Composites Inspired By Peacock Mantis Shrimp, Nandati Shrestha

Thinking Matters Symposium

The fist-like club of the peacock mantis shrimp, a 5-inch marine crustacean, can strike its prey with speed faster than a .22-caliber bullet with an impact force more than 1,000 times its own weight. Although these creatures punch so fast that it even boils the water, they don’t take any damage. This incredible insusceptibility is due to the arrangement of mineralized fiber layers in which each fibrous layer is laid at a slightly rotated angle to form a helicoidal structure that acts as a shock absorber for the club. The goal is to perform a finite element analysis ...

Mems Directional Acoustic Sensors, Colby Damren

Thinking Matters Symposium

The purpose of my project is to test and verify two Micro-Electro-Mechanical-System (MEMS) microphones. The two MEMS devices are biomimetic microphones that imitate the eardrums of the Ormia Ochracea, a parasitic fly that listens for host crickets to lay their eggs. The MEMS microphones mimic the eardrum spacing of the Ormia Ochracea with a spacing of 1000um. This is roughly twice the opening of the Ormia Ochracea. The microphones will be tested for directionality inside a wooden box. This box will be lined with beveled foam to prevent any echo or outside noise from interfering with the results. These results ...

The Discovery And Analysis Of Peroxidase Enzyme In Pueraria Montana, Kathryn Briley

Senior Honors Theses

Peroxidase enzymes are used for a variety of industrial and biotechnological applications because of their ease of purification, broad range of chemical activities, and low cost of use. Identification of quality peroxidase sources that are convenient for enzymatic isolation and give way to high yields of product is a desirable pursuit in biochemical research. Kudzu is an excellent candidate for this pursuit as it displays high catalytic activity in screening assays and is found in abundance. This project seeks to determine the enzyme stability, optimal pH conditions, and possible novel chemical activities of peroxidase isolated from kudzu leaves. The methods ...

Histone H2b Repression (Hbr) Domain Regulates Cell Cycle Progression And Dna Damage Response In The Yeast Saccharomyces Cerevisiae, Kaitlyn Galliher, Michael Parra

Senior Scholars Day

In eukaryotic genomes, DNA is packaged with a group of proteins called histones to form chromatin. The basic repeating subunit of chromatin, the nucleosome core particle (NCP), is made up of two copies each of the canonical histones H2A, H2B, H3, and H4. Though compaction allows large amounts of DNA to fit into the relatively small space of the nucleus, it establishes a physical barrier to the DNA template. Because of their close association with DNA, histones play integral roles in DNA-templated processes (e.g. transcription, DNA repair, and DNA replication). The N-terminal domain of histones H2B (amino acids 3-37 ...

Interrogating The Functions Of The Histone H2a Repression Domain In Relation To Cell-Cycle Progression In Saccharomyces Cerevisiae, Taylor Nattress

Senior Scholars Day

In eukaryotic cells, DNA is wrapped around histone proteins to form the basic repeating unit of chromatin, the nucleosome core particle. Most nucleosomes consist of two copies each of histones: H2A and H2B in a heterodimer and histones H3 and H4 in a heterotetramer. Because of their intimate association with DNA, histones regulate all DNA-templated processes such as transcription, DNA replication, and DNA damage response and repair. Several studies have illustrated the importance of a small portion of the histone H2A amino terminal domain which regulates global transcription. This domain is responsible for the repression of ~4% of the yeast ...

The Analysis Of Folate-Dependent Transcription Factor Zinc Finger Protein 410, Feifan Xu

Senior Honors Theses

A previous study that introduced dietary folate to mice in the form of folic acid to determine if gene activity would be altered based on this biological molecule demonstrated that mice without folic acid had cognition deficits, and this phenomenon was correlated with altered gene expression in their brains. The included bioinformatic analysis revealed two main transcription factors that bind to proteins in the nucleus, and one is known as the Zinc Finger Protein 410 (Zfp410). Due to the lack of literature explaining the function of this transcription factor, this project is intended to analyze Zfp410 in detail from scratch ...

216— Loss Of Function Mutation For Tp53 Does Not Rescue The Chaf1bNt2 Small-Eye Phenotype In Danio Rerio, Alex Parks

GREAT Day

In Zebrafish, the chromosome assembly factor 1b (chaf1b) gene is in part responsible for the development of the eye. In homozygous chaf1bt24412 mutants retinal cell death is promoted through cell-death promoting activity of the gene, tumor suppressor protein p53 (tp53), resulting in a small-eye phenotype. Another allele chaf1bnt2, was found to also result in the small-eye phenotype when in a homozygous state. We found that knockdown of Tp53 protein via morpholino antisense oligonucleotide injection of 1-2 cell stage embryos failed to rescue retinal cell death of chaf1bnt2 homozygous mutants as detected by TUNEL labeling. Because morpholinos may fail to fully ...

Using The Lambert Function To Map Enzyme Kinetics, Melissa Gouge

ONU Student Research Colloquium

In an academic setting, enzyme kinetics are introduced by analysis of the initial rates using the Michalis-Menten model. To better understand enzyme kinetics, a complete time course analysis will provide a larger set of information. The use of the integrated form of the rate equation allows for a beginning glance at the mechanism of reaction. With this, the Lambert Ω function can be used to analyze the integrated rate equations. There are two different branches of the Lambert Ω function, a negative branch and a positive branch. For each branch there is a unique expanded series approximation used for analysis ...