Biochemistry, Biophysics, and Structural Biology Commons^™

Missense Mutation Of Msh6 Leucine 696 Has No Apparent Effect On The Dna Mismatch Repair Process, Razan H. Hammad, Rafia Rashid, Essence Tarrence, Christopher Bolden, Joanna E. Haye-Bertolozzi

XULAneXUS

Lynch Syndrome and Constitutional Mismatch Repair Deficiency are human diseases implicated in mutations of DNA mismatch repair (MMR) genes. This experiment tested a mutation of an MMR gene, MSH6, and evaluated how the mutation affected overall MMR effectiveness. Using the yeast Saccharomyces cerevisiae, we performed the CAN1 forward mutation assay to study msh6-L696F and its implications in the MMR process. We hypothesized that there would be a significant change in molecular function in the Msh6 protein in the presence of this mutation. Bioinformatic tools predicted that this amino acid change would have deleterious effects on MMR function. However, …

Hexasodium Fytate (Snf472 Or Csl525) Inhibits Ectopic Calcification In Various Pseudoxanthoma Elasticum And Calcinosis Cutis Animal Models, Miguel Ferrer, Maria Pérez-Ferrer, Marc Blasco, Ida Jacobs, Qiaoli Li, Olivier Vanakker, Lisa Dangreau, Andrea López, Gianluca Malagraba, Firas Bassissi, Joan Perelló, Carolina Salcedo

Department of Biochemistry and Molecular Biology Faculty Papers

Background/Objectives: Ectopic calcification is a pathological condition characterized by the mineralization of soft tissues due to the deposition of calcium phosphate crystals. Hexasodium fytate (CSL525, previously known as SNF472) is a crystallization inhibitor being developed for the treatment of ectopic calcification-related disorders. Our aim was to investigate CSL525 for the treatment of soft-tissue calcification disorders in animal models of pseudoxanthoma elasticum and calcinosis cutis. Methods: In a first study, abcc6^-/- zebrafish larvae were exposed to 1 mM CSL525 for 7 days or kept under the same conditions without CSL525, and spinal mineralization was quantified. In a second study, abcc6 …

The Fractography Of Bone: Impact Of Flat Bone And The Story It Tells, Abigail Hoffmeister, Chase Freeman, Brandon Mendoza, Nathaniel Fitch, Annie Markarian, Jack Tran, Joshua Lau, Nicholas Tran

Seaver College Research And Scholarly Achievement Symposium

Fractography as a method for fracture analysis has been applied widely to materials that range from glass to ceramics and polymers of varying compositions. Very limited research has been done, however, to apply this knowledge of fractography and fracture patterns to bone. With the goal of telling the story of how a bone was broken, this research focuses on observing known patterns of fracture in polymers, and applying these patterns to bone. For the purposes of this research, porcine scapulae were acquired, dissected from surrounding tissue, and broken using a standardized weight drop at varying heights. The fractured bone was …

Diets And Environmental Impacts - Generational Outlook, Aspen Hopper, Melanie Jex

Student Research Symposium

How different diets impact the environment: Are we aware?

Determining The Kinetic Basis Of Crispr-Cas12a2 Function, Sobita Kunwar, Thomson Hallmark, Dylan Keiser, Bronson Naegle, Sudeshna Manna, Aaron Thomas, Chase L. Beisel

Student Research Symposium

CRISPR- Cas (Clustered Regularly Interspaced Short Palindromic Repeats- CRISPR associated) systems are bacterial adaptive immune systems that protect bacteria against mobile genetic elements such as viruses and plasmids^1,2.

Solving The Structure Of An Ancestral Protein Tyrosine Phosphatase, Natalie Turcsanski, Edna Armah

Student Research Symposium

Protein tyrosine phosphatases (PTPs) regulate cell signaling by removing phosphate groups from tyrosine residues. Malfunction of these enzymes can lead to diseases such as diabetes and cancer. A conserved feature among PTPs is the catalytic acid loop, essential for phosphate removal. Computational analysis of PTP structures revealed that ancestral PTPs have considerable variation in conformations of this loop, sparking interest in their further study. The Asgard group, identified as ancestral to eukaryotic PTPs, was successfully expressed and purified under optimized conditions. Current efforts focus on optimizing crystallization to obtain larger crystals for structural analysis. This project will investigate the allosteric …

Determining The Function Of Type Iv-B Crispr-Cas Systems, Eric Jenkins, Brendon Guinn

Student Research Symposium

CRISPR-Cas systems are a diverse group of prokaryotic adaptive immune systems that defend against Mobile Genetic Elements (MGEs) such as bacteriophages and plasmids. CRISPR-associated (Cas) proteins bind to guide RNAs (crRNAs) transcribed from a DNA repeat array (CRISPR array) containing spacers complementary to MGEs. Upon infection by a MGE, the Cas protein-crRNA complex binds to the target sequence in the invaders genome and cleaves the nucleic acid.

Activation Of Enkephalinergic Neurons Modulate Pain Within The Brain, Lucy N. Scribner, Oakley M. Statham, Greydon R. Durrant, Callie M. Newson

Student Research Symposium

The endogenous opioid system, consisting of three neuropeptides and canonical receptors, is ubiquitously expressed throughout the brain and is heavily involved in modulating pain[1]. However, research has placed tremendous focus on investigating the receptors of this system, and less attention has been devoted to the peptides. One such opioid peptide, enkephalin, is notably absent within the pain center of the brain, the periaqueductal gray (PAG)[2]. To further understand the role enkephalins play in modulating pain, we aimed to target and activate specific enkephalin-containing neurons that connect to the PAG. By activating these enkephalinergic projections, we hypothesized that this would lead …

Metabolite Analysis To Understand Factors Limiting Microbial Fermentation At High Substrate Concentrations, Bishal D. Sharma

Dartmouth College Ph.D Dissertations

Clostridium thermocellum, a thermophilic anaerobic bacterium, holds promise as a biocatalyst for conversion of lignocellulosic biomass into biofuels. This microbe has been subjected to various metabolic engineering strategies, including the deletion of genes encoding secondary fermentation products such as H₂, formate, acetate, and lactate, as well as the expression of heterologous genes to redirect carbon flux toward ethanol production. Despite these efforts, achieving economically viable ethanol titers remains a challenge. We hypothesized that studying how intracellular metabolite concentrations change as fermentation stops could reveal metabolic bottlenecks or regulatory mechanisms limiting ethanol production at high titers. However, metabolomics studies at …

Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …

Biochemical And Structural Insights Into The Yersinia Effector Yopm And Its Negative Regulation Of The Pyrin Inflammasome, Bethany Wairimu Mwaura

Dartmouth College Ph.D Dissertations

Bacteria utilize sophisticated secretion systems to inject effectors into host cells in order to facilitate their survival and replication in the host. Some pathogenic species of Gram-negative bacteria use a conserved contact-dependent T3SS to inject a wide array of effectors. While the effectors diverge in their structures, functions and cell-localization, the T3SS is well conserved. Several effectors discussed in this thesis target key host inflammasome responses. The focus of this work is how the Yersinia effector YopM inhibits the pyrin inflammasome. During Yersinia infection, two effectors, YopE and YopT inadvertently activate the pyrin inflammasome while targeting RhoA to avoid phagocytosis. …

Anticancer Activity Of Allium Cepa Through The Inactivation Of Nf-Κb Pathway: A Literature-Based Study, Sharmita Ghosh Situ, Md. Sakib Al Hasan, Emon Mia, Md. Nasimul Haque Shipon, Md. Faisal Amin, Asmaul Husna Bristy, Yasin Emon

School of Integrative Biological & Chemical Sciences Faculty Publications

Allium cepa (onion) is a bulbous herb renowned for its diverse health benefits. This study aims to summarize the anticancer potential of A. cepa through the inactivation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by reviewing experimental findings across various cancer models. A thorough examination of the literature was carried out using databases like Google Scholar, PubMed, Web of Science, and ScienceDirect. The findings revealed that phytochemicals such as stigmasterol, fisetin, quercetin, isorhamnetin, morin, kaempferol, luteolin, β-carotene, and β-sitosterol exhibit strong anticancer properties against various cancers, including breast, bladder, colon, colorectal, cervical, lung, liver, oral, pancreatic, …

Antioxidant Activity Of Pamam Dendrimer Stabilized Ascorbic Acid, Gabriella Srikureja

Honors Theses

Ascorbic acid (vitamin C) is an essential micronutrient for human health. It acts as an enzymatic cofactor in anabolic biochemical pathways such as the synthesis of collagen, dopamine, and norepinephrine. Unfortunately, this versatility comes at the cost of a high degradation rate both in and outside of the food matrix. Previous research exploring stabilizing aqueous ascorbic acid through Poly(amidoamine) (PAMAM) dendrimers found success in reducing the rate of degradation.

To confirm the antioxidant activity of ascorbic acid in its stabilized dendrimer complex, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assays examined via Cary 5000 UV-Vis-NIR spectrophotometer found that performing the DPPH assay under aqueous conditions …

Cytokinesis & Dbf2, Katharine Gray, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.

Carrier Analysis Of Alc Lipid Nanoparticles With Lung Cancer Drug, Noah Sparks, Lei Xu, Hu Yang

Miners Solving for Tomorrow Research Conference

No abstract provided.

Discovering Localization Of Fun19 Orf In Yeast, Megan Percy, Galayna Baur, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.

The Effects Of Preventing Dephosphorylation Of Iqg1 On Cytokinesis, Jenna L. Mueller, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.

Characterization Of An Iqg1 Phosphorylation Mutant, Lindsay Scheider, Alexis Ham, Katie Shannon

Miners Solving for Tomorrow Research Conference

No abstract provided.

Metabolic Transitions In Embryos Of Artemia Franciscana: Regulation And Consequences For Oxidative Stress, Daniel Anthony Arabie

LSU Doctoral Dissertations

Embryos of Artemia franciscana survive harsh conditions in diapause and anoxia-induced quiescence for years by undergoing deep metabolic transitions. I investigated the relationship between phosphorylation of pyruvate dehydrogenase (PDH) and carbon flux to the tricarboxylic acid (TCA) cycle during metabolic depression. The difference in catalytic activity of the PDH complex (PDC) in maximally phosphorylated and dephosphorylated samples was 16.5-fold. Western blot analysis confirmed the changes in phosphorylation of PDH. Analysis of PDH expression in diapause and post-diapause embryos via phospho-PDH showed no significant differences. Investigation of post-diapause embryos under anoxia showed that phosphorylation of PDH decreased and activated the enzyme. …

Toward Ar Visualization Of The Fluid-Mosaic Model Of The Cell Membrane, Yoonwoo Lee, Allison Ost, Junghyuk Lee, Krisztina Z. Bencze

SACAD: Scholarly Activities

Background: During the first semester of biochemistry experience, students focus on learning the structure and function of biomolecules: carbohydrates, lipids, proteins, and nucleic acids. Visualizing these structures and understanding interactions between molecules helps students better understand biological function. A variety 3D visualization tools are available, ex. PyMol, Chimera, Avogadro, Blender. Within the past decade, Augmented Reality (AR) and Virtual Reality (VR) applications gained more popularity. VR with its immersive visual experience is more sought-after, but the higher cost and the need for headset creates limitations in the classroom. AR visualizations are cheaper and more accessible, several publications report successful implementation …

Host P53 Expression During C. Parvum Infection…Does The Virus Play A Role?, Jasdeep Kaur Dhanoa

Biochemistry and Molecular Biology

C. parvum infection induces significant host cellular stress responses, particularly through the modulation of p53 expression underscoring its potential involvement in gastrointestinal malignancies. Understanding these mechanisms is crucial for developing targeted therapeutic interventions. This study investigated the effects of C. parvum infection on host p53 dynamics in HCT-8 cells and assessed the impact of antiviral agents Lamivudine and Amantadine on the virus CSpV1 present within the parasite C. parvum. Further, the study focuses on whether the p53 effect changes with the presence or absence of CSpV1. The p53 assay results showed a constant increase in p53 activity after infection of …

Resurrecting The Past: Engineering Ancestral Enzymes For Modern Bacterial Applications, Gregory M. Gladkowski Iii, Masa Watanabe

SACAD: Scholarly Activities

Ancestral Sequence Reconstruction (ASR) is a computational technique that infers and resurrects ancient protein sequences to explore molecular evolution and enable protein engineering. By integrating phylogenetics and statistical modeling, ASR produces stable, mutation-tolerant enzymes ideal for directed evolution. This poster presents a workflow for reconstructing enzymes from pathogenic bacteria and highlights ASR’s value in uncovering novel functions and advancing applications in drug discovery and synthetic biology.

Kinetic Control And Trapping In The Supramolecular Polymerization Of M-Terphenyl Bis-Urea Macrocycles, Sophya V. Garashchuk, Gamage Isuri P. Wijesekera, Isabella G. Rushton, Vaibhavi A. Samant, Fahidat A. Gbadamosi, Dr. Md Faizul Islam, Sophya V. Garashchuk, Prof. Dr. Linda S. Shimizu

Faculty Publications

Herein, we examine pathway complexity in the supramolecular polymerization of a novel m-terphenyl bis-urea macrocycle. Designed to induce kinetically metastable states, the macrocycle‘s concentration-dependent aggregation was studied via 1H NMR and IR spectroscopy in THF and CHCl₃. Temperature-dependent UV-Vis spectroscopy in water/THF revealed a cooperative nucleation-growth mechanism, indicated by a shift in λmax to longer wavelengths upon cooling. Morphological studies using DLS, AFM, and SEM demonstrated fibrous aggregate formation. Thermal hysteresis observed in assembly-disassembly cycles indicated kinetically trapped species, with cooling governed by kinetic control and heating by thermodynamic processes. Deviations in ΔH values during cooling, compared to van′t …

How The Biotic And Abiotic Factors In The Belle Forest Cave And Arboretum Soil Dictates Tree Species Prevalence, Amya A. Bingham

SPARK Symposium Presentations

A plethora of factors in the soil impact a plant’s health, including the presence of different biotic and abiotic factors. These include things like temperature, elevation, pH, microbial respiration and the presence of water, clay, loam, silt, sand, nitrogen, potassium, and phosphorus. Different soils will have varying amounts of these, which may dictate what is able to grow in them, and therefore also the surrounding area. This research project explores how the aforementioned biotic and abiotic factors affect the soil at the Belle Forest Cave and Arboretum. Three samples will be taken from four spots along a transect at this …

Proteomic-Based Strategies To Determine Aberrant Signaling In Cancer, Natasha Chipman Mariano

Dartmouth College Ph.D Dissertations

Proteomics and phosphoproteomics have emerged as powerful tools to elucidate the intricate molecular underpinnings that drive cancer development by quantifying changes in protein and post-translational modification abundances. Throughout my thesis work, I have advanced these techniques to map cancer signaling networks on a global scale. Among breast cancer subtypes, triple-negative (TNBC) remains the most challenging to treat, with poorer clinical outcomes attributed to tumor heterogeneity and yet unidentified, oncogenic driver proteins for therapeutic targeting. To identify potential targeted treatment strategies, we employed mass spectrometry-based quantitative proteomics to analyze 55 formalin-fixed paraffin- embedded TNBC tumor specimens. Unsupervised hierarchical clustering of relative …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …

College Of Natural Sciences Newsletter, Spring 2025, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message from Dr. Sen Subramanian
Page 2 Student Spotlights
Page 3 Kaushik honored, Three-Minute Thesis, & Ice Cores revealed
Page 4 Alumni Spotlight
Page 5 Day of Scholars
Page 6 Cyanide research, Record Research Expenditures, Adhikari awarded Miller Research Award
Page 8 Hanson Receives NSF Grant
Page 9 Snow Lab Research Team
Page 10 Faculty Awards
Page 11 Drone Day
Page 13 Khalaf Awarded Presidential Award

Next-Generation Biomedical Implants And Stimuli Responsive Soft Optical Arrays Via Surface Functionalized Elastomeric Materials, John M. Kapitan

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The demands of emerging technologies, such as soft robotics, stretchable electronics, and next generation biomedical implants, has led to the development of diverse polymeric and hybrid organic/inorganic materials specifically tuned to meet these challenges. These materials typically have low Young’s moduli and are inert with high chemical stability. However, this has led to materials that are static in nature, lacking any meaningful way of responding to changes in their environment and adapting to these changes. This has driven a shift towards the design, manufacturing, and characterization of various stimuli responsive surfaces, relying on precise control of surface chemical coatings and …

Dental Disparities: An Analysis Of Dental Caries Risk Factors Promoting Disparities Between Rural And Urban Communities In Nebraska, Nick Lounsbery

Honors Program: Senior Projects (Public)

The prevalence of dental caries in the United States remains a public health concern, as it is one of the most common chronic conditions across people of all ages. Research shows that preventative measures including brushing, fluoridated water, and regular checkups are effective strategies to mitigate tooth decay. However, there appears to be a divide between rural and urban populations, as the presence of dental cavities is significantly greater in remote areas in the State of Nebraska. Research methods used in this analysis included analyzing accredited academic literature to illustrate how cavities form from a biochemical perspective. Research methods also …

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …