Biochemistry, Biophysics, and Structural Biology Commons^™

Assessment Of Histone Acetyltransferase Homologs In Cryptococcus Neoformans, Phoebe Bridy, Felice Kho, Yuqi Wang

Liberty University Research Week

Undergraduate

Basic

Rescue Of Glutaric Aciduria Type I In Mice By Liver-Directed Therapies, Mercedes Barzi, Collin G Johnson, Tong Chen, Ramona M Rodriguiz, Madeline Hemmingsen, Trevor J Gonzalez, Alan Rosales, James Beasley, Cheryl K Peck, Yunhan Ma, Ashlee R Stiles, Timothy C Wood, Raquel Maeso-Diaz, Anna Mae Diehl, Sarah P Young, Jeffrey I Everitt, William C Wetsel, William R Lagor, Beatrice Bissig-Choisat, Aravind Asokan, Areeg El-Gharbawy, Karl-Dimiter Bissig

Faculty, Staff and Students Publications

Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabolites in the brain are produced locally and do not cross the blood-brain barrier. In a series of experiments using knockout mice of the lysine catabolic pathway and liver cell transplantation, we uncovered that toxic GA-1 catabolites in the brain originated from the liver. Moreover, the characteristic brain and lethal phenotype of the GA-1 mouse model was rescued by two different liver-directed gene therapy …

Study Of Protein Extraction Techniques For M. Foliorum Phages, Lola Sibaud, Anna Elgersma

Student Academic Conference

Characterizing phages is becoming increasingly important in biochemistry and biotechnology due to their potential to treat bacterial infections without need for antibiotics. Last year, students attempted to isolate proteins from Microbacterium foliorum infecting phages Babydotz and Rosadiaz. Proteins were successfully extracted; however, after further analysis it was shown that the obtained proteins belonged to the host bacteria and not the phages. The purpose of this study was to find a method to separate phage from host bacterial debris to successfully isolate phage proteins and analyze them later. Isolating phage proteins could help us characterize more phages and know more about …

Novel Plant Peroxidase Investigation For Use In Various Biochemical And Practical Applications, Sally Hess

Liberty University Research Week

Undergraduate

Basic

Activation Of Nrf2 Pathway By Natural Products, Genesis Schat, Madelyn Sedlachek

Liberty University Research Week

Undergraduate

Basic

Characterization Of A Sas3 Homolog In The Human Pathogenic Yeast Cryptococcus Neoformans, Lillianne Bartone

Liberty University Research Week

Undergraduate

Basic

Characterization Of Select Lysine Mutations Of The Cystine/Glutamate Transporter, System XC-, Anna Koppin, Claire Buck, Amanda Gibson

22nd Annual Celebration of Undergraduate Research and Creative Activity (2023)

System xc- is a membrane transport system that plays a critical role in mitigating oxidative stress. As such, its regulation is critical for proper brain functioning. Recent work in our lab has shown that System xc- activity increases immediately during an oxidative insult by undergoing a change in localization to the plasma membrane, but we have yet to identify the specific mechanism for the redistribution of the transporter. Previous studies have demonstrated that post-translational modifications of proteins can lead to differential protein distribution within cells. Therefore, in this study, we sought to determine if post-translational modification (PTM) of the transporter …

Does Phosphorylation On Serine 26 Of System Xc- Lead To Changes In Cell Surface Expression?, Katherine Lane

22nd Annual Celebration of Undergraduate Research and Creative Activity (2023)

System x_c^- is involved in transporting cystine into cells and glutamate out of cells, and ultimately in production of the antioxidant glutathione. Antioxidants are important in protecting cells from oxidative stress which can occur when waste products like H₂O₂ build up in the cell. Previous studies have shown that a critical regulator mTORC regulates system xc- by phosphorylating serine 26 (S26) on the N-terminus of the cystine/glutamate antiporter xCT, leading to a reduction in transport activity. The specific objective of this study is to determine the mechanism by which phosphorylation of S26 affects activity. To …

Creation Of An N-Terminal Xct Mutant Lacking Lysines For Use In Protein Turnover Studies, Alexandria Switzer

22nd Annual Celebration of Undergraduate Research and Creative Activity (2023)

xCT plays a role in protecting cells from oxidative stress as well as intracellular glutathione synthesis. If this process is impeded, reactive oxygen species accumulate in the cell, leading to cellular damage, and if left unchecked, it can lead to neuronal loss. Ubiquitin is a small protein that some evidence suggests can negatively affect the stress response pathway modulated by xCT, as well as induce cell death. It is hypothesized that ubiquitin binds to xCT on the N-terminal lysine residues, and there are six conserved lysines in the N-terminal domain at positions K4R, K12R, K30R, K37R, K41R, and K43R. Previous …

Early Life Δ9-Tetrahydrocannabinol Exposure Of F0 Zebrafish Causes Hyperactivity In F1 Offspring, Jenna Cripe

Honors Theses

As cannabis increases in its accessibility, potency, and acceptance across the United States, investigation into the multigenerational effects of Δ9-tetrahydrocannabinol (THC) exposure during key stages of development is critical. The aim of this study was to evaluate whether there would be behavioral impacts in the F1 offspring following a dose-response of THC exposure (0.08, 0.4, or 1 µM) during development in the F0 generation. Zebrafish (Danio rerio) were utilized in this study. Behaviors (locomotive activity and anxiety-like behavior) in the F1 generation were evaluated at 120 hours post-fertilization (hpf) with the larval photometer response (LPR) assay, and at 3, 11, …

A Fisher Indole Synthesis Approach To Phidianidine Analogues, Anna Tingler, Trinity Ghering, Samuel Ross

Undergraduate Research Competition

Naturally occurring products are molecules that are found in the natural world without the aid of humans. Aspirin and opium are famous examples of this classification of molecule. Another example of natural products that are less known are the phidianidines. Phidianidines A & B were isolated from a shell-less mollusk, Phidiana militaris. These molecules are comprised of a 1,2,4-oxadiazole ring, an indole and an aminoalkylguanadio group. These compounds have exhibited striking pharmacological behavior such as that of neutralizing reactive oxygen species and acting as an agonist for the μ-opioid receptor. In recent years, the synthesis of phidianidine analogues has replaced …

A New Approach To The Core Of Flinderole C, Ana Pettijohn, Claire Romain

Undergraduate Research Competition

The flinderoles A-C are a class of anti-malaria bisindole alkaloids from plants of the Flindersia genus. Flinderole C was specifically from the Papua New Guinean plant called F. amboinensis and is the most potent antimalarial of the group. Malaria is a parasitic infectious disease usually found in the hot, tropic regions of the world, such as parts of Africa. It is estimated that nearly half the world's population lives in an area where it is endemic. Furthermore, malaria was estimated to have caused over 600,000 deaths in 2020. While measures to limit the spread of the disease lessen its impact, …

Discovery And Characterization Of A Prophage Encoded Anti-Crispr Against The Type Iv-A Crispr System, Andrew Williams

Student Research Symposium

CRISPR Systems are adaptive immune systems in bacteria used to defend against mobile genetic elements such as bacteriophages, or bacterial viruses, and plasmids. They use a protein complexed with a guide RNA to target the protein to a foreign invader and neutralize it by cleaving its genetic information. In order to survive and keep infecting bacteria, bacteriophages likewise have developed machinery used to inhibit CRISPR immunity in the form of anti-CRISPR (Acr) proteins. The type IV-A system is a recently discovered and characterized system by the Jackson lab. It has been shown to defend against plasmids, but further data on …

Cycloaddition Of Aryldiazoacetates With Terminal Alkynes And Nitriles Via A Bioinspired Cobalt Complex, Liming Tan

Student Research Symposium

In this study, we present a novel method for the efficient cycloaddition of aryl diazoacetates with both terminal alkynes and nitriles, employing a bioinspired cobalt complex as a catalyst. Our findings indicate that terminal alkynes react with aryl diazoacetates to yield a cyclopropenation product through a 2+1 cycloaddition reaction. Meanwhile, nitriles react with aryl diazoacetates to produce an oxazole product via a 2+3 cycloaddition reaction. These results have significant implications for the development of new synthetic routes towards cyclopropenation and oxazole compounds.

Developing A Safe And Effective Papillomavirus Screen To Be Used On College Students, Nicole Frantz

Undergraduate Research Competition

Human papillomavirus (HPV) is the most common sexually transmitted infection that accounts for approximately 5% of all cancers worldwide and affects more than 80 million people in the US alone, according to the CDC and National Cancer Institute. Human papillomaviruses are small, nonenveloped, icosahedral DNA viruses that infect squamous epithelial cells. The viral particles consist of a single double stranded DNA molecule bound to histones and contained within a protein capsid composed of structural proteins late (L)1 and L2. To date, over 100 different genotypes of HPV have been identified, and approximately 15 types are considered oncogenic in cervical, vulvar, …

Environmental Bacteriophage Presence In The Drainage Ponds At Coastal Carolina University, Alexei Chesnutwood

Undergraduate Research Competition

The purpose of this research is to detect naturally occurring, lytic bacteriophages and identify the environmental factors that influence their presence on Coastal Carolina University’s campus. Bacteriophages are non-living viruses that only infect bacteria, and these viruses are found in abundance in every environment. Likewise, coliphages are viruses that exclusively infect coliform bacteria. Eleven treated and untreated freshwater sample sites were chosen for weekly sampling on CCU’s campus. During water sample collection, ambient environmental conditions were measured. In addition, precipitation was tracked over the collection period as runoff relates to the proliferation of bacteriophages. If plaque assays indicated the presence …

Toward Quantification Of Hypoxia Using Fluorinated Euii/Iii-Containing Ratiometric Probes, S A Amali S Subasinghe, Caitlyn J Ortiz, Jonathan Romero, Cassandra L Ward, Alexander G Sertage, Lyazat Kurenbekova, Jason T Yustein, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia is a prognostic biomarker of rapidly growing cancers, where the extent of hypoxia is an indication of tumor progression and prognosis; therefore, hypoxia is also used for staging while performing chemo- and radiotherapeutics for cancer. Contrast-enhanced MRI using EuII-based contrast agents is a noninvasive method that can be used to map hypoxic tumors, but quantification of hypoxia using these agents is challenging due to the dependence of signal on the concentration of both oxygen and EuII. Here, we report a ratiometric method to eliminate concentration dependence of contrast enhancement of hypoxia using fluorinated EuII/III-containing probes. We studied three different …

A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral And Cellular Immune Responses And Protects Mice From Lethal Virus Challenge, Aryamav Pattnaik, Bikash R. Sahoo, Lucas R. Struble, Gloria E. O. Borgstahl, You Zhou, Rodrigo Franco, Raul G. Barletta, Fernando A. Osorio, Thomas M. Petro, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain–Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that …

Moderate-Intensity Exercise Improves Mesenteric Arterial Function In Male Uc Davis Type-2 Diabetes Mellitus (Ucd-T2dm) Rats: A Shift In The Relative Importance Of Endothelium-Derived Relaxing Factors (Edrf), Md Rahatullah Razan, Said Amissi, Rifat Ara Islam, James L. Graham, Kimber L. Stanhope, Peter J. Havel, Roshanak Rahimian

School of Pharmacy Faculty Articles

The beneficial cardiovascular effects of exercise are well documented, however the mechanisms by which exercise improves vascular function in diabetes are not fully understood. This study investigates whether there are (1) improvements in blood pressure and endothelium-dependent vasorelaxation (EDV) and (2) alterations in the relative contribution of endothelium-derived relaxing factors (EDRF) in modulating mesenteric arterial reactivity in male UC Davis type-2 diabetes mellitus (UCD-T2DM) rats, following an 8-week moderate-intensity exercise (MIE) intervention. EDV to acetylcholine (ACh) was measured before and after exposure to pharmacological inhibitors. Contractile responses to phenylephrine and myogenic tone were determined. The arterial expressions of endothelial nitric …

Locomotor Biomechanics In Stream Gobies, Rhinogobius Sp.: Functional Performance Of Waterfall-Climbing Behavior, Ernest W. Murphy

Student Scholar Showcase

Gobiidae is the taxonomic classification of a large fish family comprising over 2,000 species. A few goby species have the unique ability of scaling waterfalls using pelvic fins that are fused into a suction disc (pelvic sucker) located on the ventral side of the body, aiding them in upstream migration to freshwater feeding and reproduction locations. This study aimed to investigate the locomotor biomechanics of Rhinogobius goby fish due to the lack of literature in the area. In particular, climbing performance variables (pressure differential, force, endurance, and kinematics of attachment), pelvic sucker fatigability, and ontogenetic patterns of physical development and …