Biochemistry, Biophysics, and Structural Biology Commons^™

Microtubule Self-Organization With Active And Passive Crosslinkers, Prashali Chauhan

Dissertations - ALL

Humans have always been trying to unravel principles that guide how things around us function, all the way from galactic ovements to basic building blocks of matter. The physical and chemical properties of ‘biological’ systems govern processes all the way from molecular interactions of proteins to the form and function of individual living organisms. In this work, I focus on the proteins which help give shape and structure to the smallest building block of life, the cell and associated mechanisms of building fundamental cellular architectures, like the mitotic spindle. Mitosis takes place by microtubules aligning themselves in anti-parallel fashion with …

Developing A Tool To Measure Resistance To Sustainable Food Choices: A Pilot Study In Ireland And The Netherlands, Kate Flanagan, Bart Sinteur, Patricia J. Bulsing, John M. Kearney

SURE Journal: Science Undergraduate Research Experience Journal

Consumer uptake of a sustainable diet is critical for addressing environmental challenges and promoting public health. Understanding why consumers resist adopting sustainable eating habits can inform targeted interventions and policies. This pilot study examines whether a newly developed scale can effectively detect consumer resistance to a sustainable diet. Currently, there is a lack of research on a tool to measure consumer resistance to a sustainable diet, highlighting the need for a reliable instrument.

The aim of this study is to develop a scale, based on existing literature, to measure consumer resistance to a sustainable diet. Additionally, the study aims to …

Editorial-Sure Journal Volume 7, Issue 2, Geraldine M. Dowling, Eva Campion, Sinead Loughran, Ariane Perez-Gavilan, Josephine Treacy

SURE Journal: Science Undergraduate Research Experience Journal

No abstract provided.

Discovery Of 5‑Chlorotryptophan-Containing Antibiotics Through Metabologenomics-Assisted High-Throughput Screening, Chantal D Bader, Isao Masuda, Angela Nichols, Edward Kalkreuter, Dong Yang, Thomas Christian, Yuko Nakano, Ya-Ming Hou, Ben Shen

Department of Biochemistry and Molecular Biology Faculty Papers

Actinomycetota bacteria have specialized in the biosynthesis of antibacterial natural products (NPs), and extract and fraction libraries made from those strains remain a promising source of NP drug leads. Herein, we present a high-throughput screen (HTS), based on engineered Escherichia coli strains expressing the human (Trm5) or bacterial (TrmD) m¹G37 tRNA methyltransferase, to discover NPs as novel anti-Gram-negative antibiotic leads. To harness the evolution of NPs with in vivo activity, the cell-based phenotypic HTS was applied to the Actinomycetota extract and fraction library at the Natural Products Discovery Center (NPDC), the Herbert Wertheim UF Scripps Institute for Biomedical …

Energetics And Kinetics Of Alkali Ion Exchange In Analcime, Jinyi Liu, An T. Ta, R. Seaton Ullberg, Jean Wilfried Hounfodji, Michael Badawi, Hans Conrad Zur Loye, Simon R. Phillpot

Faculty Publications

We employ density functional theory calculations to investigate the energetics and diffusion mechanisms of alkali metal ions (Na⁺, K⁺, Rb⁺, and Cs⁺) within the analcime framework. While Na⁺preferentially adsorbs at the center of the 8-member ring, DFT calculations show that larger ions, such as Cs⁺, occupy the center of the cage due to steric constraints. The computed exchange energies indicate that exchange of Na⁺by Cs⁺is thermodynamically favorable. Migration energy barriers, determined using the climbing image nudged elastic band method, show that Na⁺is …

Role Of Nadph Oxidase 4 In Murine Cancer-Associated Fibroblast, Faith M. Gomez

Theses & Dissertations

Breast cancer is the second leading cause of cancer deaths in women in the United States. Frontline hormone therapies for breast cancer prove ineffective in triple negative breast cancer tumors wherein the hormones estrogen, progesterone, and HER2 are downregulated or absent; therefore, patients diagnosed with triple negative breast cancer are primarily limited to chemotherapies which carry a higher failure and resistance rate. Here we target cancer associated fibroblasts as potential drivers of chemoresistance in triple negative breast cancer. We investigated the mechanism by which Nox4 regulates the YAP/TAZ pathway in modulating DTX sensitivity and sought to determine if targeting Nox4 …

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 …

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 …

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 …

Levels Of Beta Catenin With Treatment Of Hd5 In Iec-6 Rat Cells, Audrey Birdwell, Josiah Stafford, Obaid Ashari, Emily Powell, Maryam Gerges, Maryam Mina

Student Scholar Symposium

Human Defensin 5 (HD5) is an antimicrobial peptide present in the small intestine that plays a role in gut homeostasis. We have been investigating the role of HD5 in colon cells, but research shows that HD5 levels in the small and large intestine vary significantly in Crohn's. Previous data from our lab suggests that HD5 leads to a decrease in wound healing and an increase in apoptosis in colon cells, we want to see if the same is true in the small intestine. So, we are investigating the effect of HD5 on expression of β-catenin, a key protein in the …

Understanding The Role Of Hd5 In Colonic Epithelial Cell Death, Maryam M. Gerges, Amanda D. Williams

Student Scholar Symposium

Inflammatory bowel disease (IBD) is an autoimmune disorder where the immune system attacks healthy tissue. IBD can occur in both adults and children, describing Ulcerative Colitis (UC) and Crohn’s Colitis (CC). Our lab studies human alpha defensin 5 (HD5), an antimicrobial peptide that normally maintains small intestinal sterility. However, in CC patients, HD5 is overexpressed in the colon. Preliminary data suggests that HD5 increases colonic cell death. This project aims to determine if HD5 induces apoptosis and its mechanisms. To this end, we will test if the suppression of caspase enzymes with a pan-caspase inhibitor reduces cell death triggered by …

Functionality Of The Ryanodine Receptor Type 1 (Ryr1) In The Development Of Malignant Hyperthermia (Mh), Cesar Medina, Joshua Owens

Student Scholar Symposium

Malignant Hyperthermia (MH) is a rare but potentially lethal pharmacogenetic disorder, affecting roughly 1 in 30,000 children and 1 in 100,000 adults undergoing surgery. MH can be triggered by agents used for general anesthesia. These may include volatile anesthetics such as sevoflurane, isoflurane, desflurane, halothane or depolarizing neuromuscular blockers such as succinylcholine. Upon administration of a trigger, an MH susceptible (MHS) patient can develop a hypermetabolic state during the intraoperative or postoperative periods. If not treated quickly, an MH episode could result in organ dysfunction or death. The primary mechanisms involved in the development of an MH crisis include the …

Elucidating The Effects Of Hd5 On Actc1 Expression In Crohn's Disease, Carolyn Tran, Sohir Abdelnour, Joyce Lawson, Ellis Puscas

Student Scholar Symposium

Approximately 1.6 million Americans currently have Crohn’s Disease (CD), a condition that affects the gastrointestinal (GI) tract, particularly the small intestine, leading to chronic inflammation, abdominal pain, severe diarrhea, and fatigue. Although treatments exist, misdiagnosis remains a challenge due to symptom overlap with other inflammatory bowel diseases (IBD). Previous studies have shown an increase in Human Alpha Defensin (HD5) in Crohn’s Colitis, resulting in slower wound healing closure, increased apoptosis, and potential effects regarding alpha-actin expression. However, its effects in the small intestine remain unclear. Alpha-actin is a cytoskeletal protein that maintains cellular structure through cell migration, tissue remodeling, and …

Have You Had Your Vitamins Today? Development Of An Lc-Ms/Ms Method With A 100% Aqueous Gradient To Simultaneously Measure B Vitamins In Plasma From Study Participants In A “Greens” Nutritional Supplement Clinical Trial, Kennedy Brothers, Abigail Davis, Anna Losher, Yusra Ahmed, Sora Ghanem, Matthew J. Vergne

Student Scholar Symposium

This study assessed the absorption of key micronutrients from the multi-ingredient supplement using a novel developed LC-MS/MS method capable of analyzing B vitamins in a single run.

The study a randomized, double-blind, placebo-controlled crossover trial with 16 healthy participants (8 males, 8 females) to measure plasma nutrient appearance over 8 hours after supplement consumption. Serial blood samples were collected pre-consumption and at specified intervals post-ingestion. The novel LC-MS/MS method simultaneously quantified biotin, nicotinamide, pyridoxine, riboflavin, and thiamin in blood samples.

Results:The LC-MS/MS method had a range of 0.1 ng/mL to 1000 ng/mL and it proved to be robust and …

Structural Basis Of A Class Ii Ribonucleotide Reductase Found If Mycobacterium Tuberculosis, Leah Jacob

Student Scholar Symposium

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health challenge, particularly due to its ability to enter a dormant, drug-tolerant state that enables long-term persistence within the host. Just before dormancy, Mtb replicates its entire genome creating DNA precursors for when the infection reactivates. Ribonucleotide reductases (RNRs) play a critical role in bacterial survival by catalyzing the conversion of ribonucleotides into deoxyribonucleotides, a necessary step for DNA replication and repair. The class II RNR, NrdZ, has been implicated in facilitating Mtb persistence under hypoxic stress conditions, yet its structural and mechanistic function remains largely uncharacterized. …

Unmasking Metals: Icp-Oes Detection Of Toxins In Costume Jewelry, Bailee Kirk, Sierra Beck, Jesse Lampley

Student Scholar Symposium

The presence of toxic trace metals in costume jewelry poses potential health risks and raises environmental concerns. Many inexpensive jewelry items contain harmful elements such as lead, cadmium, nickel, and arsenic, which can cause skin irritation, allergic reactions, and systemic toxicity through prolonged exposure. Regulatory guidelines exist to limit these metals in consumer products, but compliance varies, necessitating continued monitoring. This study utilizes Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) to detect and quantify trace metals in costume jewelry. ICP-OES offers high sensitivity and multi-element analysis capabilities, making it an effective tool for evaluating the composition of complex materials. Jewelry …

Design, Synthesis And Biological Activities Of N-Substituted Phthalimide Derivative, Beaula Mangundah

Honors Theses

Phthalimides are a group of compounds among bicyclic non-aromatic nitrogen heterocycles that have gained recognition for their bioactivity across various fields, notably anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory. This study discusses the synthesis of a novel phthalimide derivative and provides an analysis of its biological activity. It was conducted through a Boric acid Imide synthesis and yielded a successful derivative using hexylamine. The product was evaluated in vitro for antimicrobial, anticoagulant, and anti-inflammatory properties using Kirby-Bauer disk diffusion, clotting time, hemolysis inhibition, and protein denaturation assays. It showed mild anticoagulant and anti-inflammatory activity.

Methods For The Discovery Of Antibodies Toward Junin Virus Utilizing Yeast Surface Display, Jonathon E. Corral

Doctoral Dissertations and Projects

The importance of this study is to perform antibody discovery as a means to derive novel preventative and therapeutic antibody countermeasures against the Junín virus, to alleviate the potential risk of a global pandemic. The purpose of this methodological study was to develop a protocol that utilizes yeast surface display to discover antibodies, from naïve human antibody libraries, that can bind the Junín Virus antigen. The methodology of yeast surface display employs the galactose-inducible GAL1 promoter to synthesize and express antibody proteins bound to the Aga2p and Aga1p and anchored to the cell wall by glycosyl phosphatidylinositol motif (GPI). The …