Biochemistry, Biophysics, and Structural Biology Commons^™

Correlation Between Salivary Levels And Tissue Expression Status Of Her2 In Breast Cancer Patients - A Cross-Sectional Study, Arthi Sri A.S, Massillamani F, Vinothkumar Thilla Sekar

Annual Research Symposium

The study aims to investigate if soluble salivary human epidermal growth factor receptor-2 (HER2) would play a role in the diagnosis of breast cancer patients and also to find out the influence of demographic and hormonal factors on the salivary HER2 levels in breast cancer.

Investigating Optimal Laboratory Growth Conditions Of Gracilibacillus Halotolerans In Media Supplemented With Salt, Isaac Young

Annual Research Symposium

As interest continues to grow in the field of persister cells and their morphology, there arises an ever-evolving desire to further understand specific strains of bacteria that exemplify the qualities of seemingly anomalous survival regardless of anti-bacterial treatment. In the case of the Gracilibacillus halotolerans, a halotolerant extremophile extracted from the Great Salt Lake with known persistent characteristics, uncovering its optimal growth conditions was essential for future investigations. Identifying the optimal salinity for the growth of G. halotolerans will allow us to standardize our growth methods, uncover several mechanisms of saline tolerance, and add to future investigations of persistence with …

Historical Analysis Of Urban Dust Generated By The Great Salt Lake Playa, Callum Flowerday, Jaron C. Hansen, Rebekah Stanley, Kaitlyn Brewster

ScholarsArchive Data

Historical PM10 filters, provided by the Utah Division of Air Quality, were analyzed for elemental composition of various metals. This was done using ICP-MS.

Also included, EPA PM10 historical data and bathymetry data provided by the Utah USGS.

An Observational Framework For Constructing Ozone Isopleths From Long-Term Monitoring Data: Demonstration In Salt Lake City, Utah, Callum Flowerday, Isaac Sudweeks, Brad Adams, Jaron C. Hansen

ScholarsArchive Data

EPA quality assured data, collected by the Utah Division of Air Quality, was used for this analysis.

Unimer Suppression Enables Supersaturated Homopolymer Swollen Micelles With Long-Term Stability After Glassy Entrapment, Eric R. Williams, Christian X. Ruff, Morgan Stefik

Faculty Publications

Micelle sizes are critical for a range of applications where the simple ability to adjust and lock in specific stable sizes has remained largely elusive. While micelle swelling agents are well-known, their dynamic re-equilibration in solution implies limited stability. Here, a non-equilibrium processing sequence is studied where supersaturated homopolymer swelling is combined with glassy-core (“persistent”) micelles. This path-dependent process was found to sensitively depend on unimer concentration as revealed by DLS, SAXS, and TEM analysis. Here, lower-selectivity solvent combinations led to the formation of unimer-homopolymer aggregates and eventual precipitation, reminiscent of anomalous micellization. In contrast, higher-selectivity solvents enabled supersaturated homopolymer …

Unimer Suppression Enables Supersaturated Homopolymer Swollen Micelles With Long-Term Stability After Glassy Entrapment, Eric R. Williams, Christian X. Ruff, Morgan Stefik

Faculty Publications

Micelle sizes are critical for a range of applications where the simple ability to adjust and lock in specific stable sizes has remained largely elusive. While micelle swelling agents are well-known, their dynamic re-equilibration in solution implies limited stability. Here, a non-equilibrium processing sequence is studied where supersaturated homopolymer swelling is combined with glassy-core (“persistent”) micelles. This path-dependent process was found to sensitively depend on unimer concentration as revealed by DLS, SAXS, and TEM analysis. Here, lower-selectivity solvent combinations led to the formation of unimer-homopolymer aggregates and eventual precipitation, reminiscent of anomalous micellization. In contrast, higher-selectivity solvents enabled supersaturated homopolymer …

Evidence That Aquaporin 11 (Aqp11) In The Spiny Dogfish (Squalus Acanthias) May Represent A Pseudogene, Christopher P. Cutler, Meghan Canicatti, Esosa Omoregie

Biology: Faculty Publications

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148 bp fragment showing particularly strong amplification in gill and intestine. It was sequenced and represented a piece of the …

Use Of Dft Calculations As A Tool For Designing New Solvatochromic Probes For Biological Applications, Cynthia M. Dupureur

Educator Preparation & Leadership Faculty Works

The intramolecular charge transfer behavior of push–pull dyes is the origin of their sensitivity to environment. Such compounds are of interest as probes for bioimaging and as biosensors to monitor cellular dynamics and molecular interactions. Those that are solvatochromic are of particular interest in studies of lipid dynamics and heterogeneity. The development of new solvatochromic probes has been driven largely by the need to tune desirable properties such as solubility, emission wavelength, or the targeting of a particular cellular structure. DFT calculations are often used to characterize these dyes. However, if a correlation between computed (dipole moment) and experimentally measured …

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …

An Itpa Enzyme With Improved Substrate Selectivity, Nicholas E. Burgis, Kandise Vanwormer, Devin Robbins, Jonathan Smith

Chemistry and Biochemistry Faculty Publications

Recent clinical data have identified infant patients with lethal ITPA deficiencies. ITPA is known to modulate ITP concentrations in cells and has a critical function in neural development which is not understood. Polymorphism of the ITPA gene affects outcomes for both ribavirin and thiopurine based therapies and nearly one third of the human population is thought to harbor ITPA polymorphism. In a previous site-directed mutagenesis alanine screen of the ITPA substrate selectivity pocket, we identified the ITPA mutant, E22A, as a gain-of function mutant with enhanced ITP hydrolysis activity. Here we report a rational enzyme engineering experiment to investigate the …

College Of Natural Sciences 2023 Year-End Publication, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Page 1 Dean's Message
Page 3 Department Highlights
Page 4 One Day for State
Page 5 Noble Prize Winner Speaks on Campus
Page 6-7 Faculty Excellence
Page 8-9 Student Excellence
Page 10 Outreach Program
Page 10 Events and Traditions
Page 11 Connections Abroad
Page 12 Student Spotlight
Page 13 Alumni Spotlight
Page 14 First Ever Drone Day
Page 15 Grand Opening of POET Bioproducts Center
Page 16 Work Anniversaries

Mitochondrial Quality Control By Tail-Anchored Proteins, Jose M. Delgado

Dartmouth College Ph.D Dissertations

Autophagy is a lysosome-mediated pathway responsible for the degradation of unwanted cytosolic content. During autophagy, cytoplasmic components are enveloped by a newly generated vesicle (the autophagosome), trafficked to the lysosome, and degraded. The power of autophagy lies in its ability to selectively target specific substrates for degradation—a phenomenon known as selective autophagy.

Specialized proteins known as selective autophagy receptors play a crucial role in identifying and targeting autophagy cargo. Although historically overlooked as potential regulators, our understanding of autophagy receptors is evolving beyond the assumption that receptors merely bridge targets to pre-formed autophagosomal membranes. Previous insights were often based on …

Cold-Inducible Rna Binding Protein Impedes Breast Tumor Growth In The Pymt Murine Model For Breast Cancer, Daniel A. Lujan, Joey L. Ochoa, Ellen J. Beswick, Tamara A. Howard, Helen J. Hathaway, Nora I. Perrone-Bizzozero, Rebecca S. Hartley

Markey Cancer Center Faculty Publications

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse …

Biomolecular Crystals As Functional Materials, Fahmeed Khan Sheehan

Dissertations, Theses, and Capstone Projects

The field of supramolecular chemistry has undergone significant evolution over the last few decades, progressing from fundamental studies of self-assembling systems to the rational design of functional materials with exceptional properties. Among these materials, short peptides have emerged as a chemically simple yet highly versatile class of biomimetic compounds. Initially, short peptides were used as model systems to understand larger protein interactions. As the field progressed, short peptides were found to have exceptional functionality, and are now explored as functional nanomaterials for diverse applications. In many cases, short peptide materials have displayed properties not found in biology, in some cases …

Comparative Analysis Of A Secondary Metabolite Profile From Roots And Leaves Of Iostephane Heterophylla By Uplc-Ms And Gc-Ms, Diana V. Navarrete-Carriola, Alma D. Paz-González, Lenci K. Vázquez-Jiménez, Erick De Luna-Santillana, María A. Cruz-Hernández, Debasish Bandyopadhyay, Gildardo Rivera

School of Integrative Biological & Chemical Sciences Faculty Publications

Iostephane heterophylla is a traditional Mexican medicinal plant and is an important source of secondary metabolites with antimicrobial and cytotoxic activity. The aim of this work was to conduct a comparative analysis of secondary metabolites of different roots and leaf extracts of I. heterophylla from two zones in Mexico using ultraperformance liquid chromatography (UPLC) and gas chromatography (GC) coupled with mass spectrometry (MS). Twelve secondary metabolites from roots were identified in the leaves. Five new molecular weight secondary metabolites not previously reported were found. Six bioactive metabolites were quantified (quercetin ≤0.151 mg/mL in root and ≤0.041 mg/mL in leaf; hesperidin …

Mechanistic And Engineering Studies Of Lov Photoreceptors In Yeast, Matthew M. Cleere

Dissertations, Theses, and Capstone Projects

A variety of cellular biosensors have evolved which can translate electromagnetic radiation from the environment into biological functions. Light-Oxygen-Voltage (LOV) domains in particular, are a group of photoreceptors that respond to blue wavelengths of light and can become a cellular photoswitch by converting this stimulus through their attached effector domains. For instance, the Helix-Turn-Helix (HTH) DNA-binding activity of the bacterial transcription factor EL222 and the Regulator of G-protein Signaling (RGS) in the fungal membrane associating protein BcLOV4 are both induced by blue-light sensing LOV domains. While previous work has provided the field with a structural characterization of LOV proteins in …

Comparative Animal Mucomics, Antonio R. Cerullo

Dissertations, Theses, and Capstone Projects

Mucus is one of Nature’s most abundant and versatile biomaterials. These secretions are present in all animals, from the lowly garden snail to the great blue whale, and fulfill a multitude of functions, acting as antimicrobial barriers, moisturizers, adhesive glues, surface lubricants, and mineralizing agents. Despite their importance, very little is known about mucus compositions or properties. The largest challenge precluding the greater understanding of mucus function is its complexity; a single mucus contains complex mixtures of proteins, glycans, and ions that all have important roles in function. Therefore, understanding mucus function necessitates analysis that compares different mucus from one …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

Studying The Genes And Conditions That Influence Root Development, Tessa Holtkamp, Hannah Ordonez Webb

Undergraduate Research Symposium

Root development in plants is essential for their survival and understanding how hormones influence their development can explain how plants grow under different circumstances. Researching how Indole-3-butyric acid (IBA), a hormone that induces root production, affects the plant model Arabidopsis thaliana helps explain the hormone's effect in agricultural crop systems. To understand root pathways, we performed assays on mutant lines of Arabidopsis by growing plants on varying concentrations of IBA. For wild-type and mutant lines, phenotyping experiments like branching of roots, lengths of stems, and root length were conducted along with PCR and restriction digest genotyping experiments to compare their …

Investigation Of Alzheimer’S Amyloid-Β Protein Aggregation With A New Fluorescent Dye., Emma Alberty

Undergraduate Research Symposium

Alzheimer’s Disease (AD) is the most common form of dementia characterized by the impairment of at least two brain functions such as memory loss and judgement. AD is a progressive illness that can last as many as 20 years. AD is largely considered to be caused by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. A better understanding of the structure and function of these plaques may lead to clearer understanding of the disease. To analyze amyloid plaques, aggregation assays are often used. During these assays we begin with monomer and place the sample in biological conditions to …

Chromosome‑Level Assembly And Analysis Of Camelina Neglecta: A Novel Diploid Model For Camelina Biotechnology Research, Shuo Wang, Rostislav Y. Blume, Zhi‑Wei Zhou, Shaoping Lu, Tara J. Nazarenus, Yaroslav B. Blume, Weibo Xie, Edgar B. Cahoon, Ling‑Ling Chen, Liang Guo

Department of Biochemistry: Faculty Publications

Camelina neglecta is a new diploid Brassicaceae species, which has great research value because of its close relationship with the hexaploid oilseed crop Camelina sativa. Here, we report a chromosome-level assembly of C. neglecta with a total length of 210 Mb. By adopting PacBio sequencing and Hi-C technology, the C. neglecta genome was assembled into 6 chromosomes with scaffold N50 of 29.62 Mb. C. neglecta has undergone the whole-genome triplication (γ) shared among eudicots and two whole-genome duplications (α and β) shared by crucifers, but it has not undergone a specific whole-genome duplication event. By synteny analysis …

Metabolic Collaboration Between Cells In The Tumor Microenvironment Has A Negligible Effect On Tumor Growth, Johan Gustafsson, Fariba Roshanzamir, Anders Hagnestål, Sagar M. Patel, Oseeyi I. Daudu, Donald F. Becker, Jonathan L. Robinson, Jens Nielsen

Department of Biochemistry: Faculty Publications

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation, but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo. Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types. Here, we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model. In addition, we developed an approach …

The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis

Theses and Dissertations

The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …

Investigation Into Cardiacmyhc-Α 334–352-Specific Tcr Transgenic Mice Reveals A Role For Cytotoxic Cd4 T Cells In The Development Of Cardiac Autoimmunity, Meghna Sur, Mahima T. Rasquinha, Kiruthiga Mone, Chandirasegaran Massilamany, Ninaad Lasrado, Channabasavaiah B. Gurumurthy, Raymond A. Sobel, Jay Reddy

Jay Reddy Publications

Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4+ and CD8+ T cells, but defining antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57BL/6J mice specific to cardiac myosin heavy chain (Myhc)-α 334–352 and found that Myhc-α-specific TCRs were expressed in both CD4⁺ and CD8⁺ T cells. To investigate if the phenotype is more pronounced in a myocarditis-susceptible genetic background, we backcrossed with A/J mice. At the fourth …

Elastin-Like Polypeptide As A Model To Study Intrinsically Disordered Proteins, Sadegh Majdi

Theses and Dissertations

The elastin-like polypeptide (ELP) is a well-studied structural protein that is easily amenable to amino acid (AA) sequence modifications and has the potential to yield a wide variety of uses in bioengineering and biomedical applications. One unique property of ELP is the inclusion of intrinsically disordered domains (IDP) within the structure that allow for its diversity of physical properties. While it is generally understood that amino acid sequence dictates protein folding arrangements, the contributions of specific amino acid sequences to the intrinsic disorder of ELP has yet to be fully resolved. Therefore, identifying the contributions of specific amino acid sequences …

Emerging Roles Of Cullin-Ring Ubiquitin Ligases In Cardiac Development, Josue Zambrano-Carrasco, Jianqiu Zou, Wenjuan Wang, Xinghui Sun, Jie Li, Huabo Su

Department of Biochemistry: Faculty Publications

Heart development is a spatiotemporally regulated process that extends from the embryonic phase to postnatal stages. Disruption of this highly orchestrated process can lead to congenital heart disease or predispose the heart to cardiomyopathy or heart failure. Consequently, gaining an in-depth understanding of the molecular mechanisms governing cardiac development holds considerable promise for the development of innovative therapies for various cardiac ailments. While significant progress in uncovering novel transcriptional and epigenetic regulators of heart development has been made, the exploration of post-translational mechanisms that influence this process has lagged. Culling-RING E3 ubiquitin ligases (CRLs), the largest family of ubiquitin ligases, …

Unveiling The Unique Ras Isoform And Domain Specific Regulation Of Braf Kinase, Tarah Trebino

Theses and Dissertations

BRAF kinase is a key member of the MAPK pathway, important for cell growth and division. Upstream signals promote BRAF activation by interaction with the membrane bound GTPase, RAS, which leads to relief of autoinhibition and dimerization. The N-terminal regulatory domains of BRAF, including the BRAF specific region (BSR), the RAS binding domain (RBD), and the cysteine rich domain (CRD), govern the conformational state of the cytosolic, autoinhibited monomer and drive the RAS-RAF interaction. Active BRAF phosphorylates and activates its substrate MEK, which in turn phosphorylates and activates ERK. Mutations in RAS and BRAF are the cause of many cancers …

Augusta: From Rna-Seq To Gene Regulatory Networks And Boolean Models, Jana Musilova, Zdenek Vafek, Bhanwar Lal Puniya, Ralf Zimmer, Tomáš Helikar, Karel Sedlar

Department of Biochemistry: Faculty Publications

Computational models of gene regulations help to understand regulatory mechanisms and are extensively used in a wide range of areas, e.g., biotechnology or medicine, with significant benefits. Unfortunately, there are only a few computational gene regulatory models of whole genomes allowing static and dynamic analysis due to the lack of sophisticated tools for their reconstruction. Here, we describe Augusta, an open-source Python package for Gene Regulatory Network (GRN) and Boolean Network (BN) inference from the high-throughput gene expression data. Augusta can reconstruct genome-wide models suitable for static and dynamic analyses. Augusta uses a unique approach where the first estimation of …

Gene Editing Of Pigs To Control Influenza A Virus Infections, Taeyong Kwon, Bianca L. Artiaga, Chester D. Mcdowell, Kristin M. Whitworth, Kevin D. Wells, Randall S. Prather, Gustavo Delhon, Mark Cigan, Stephen N. White, Jamie Retallick, Natasha N. Gaudreault, Igor Morozov, Juergen A. Richt

School of Veterinary and Biomedical Sciences: Faculty Publications

Proteolytic activation of the hemagglutinin (HA) glycoprotein by host cellular proteases is pivotal for influenza A virus (IAV) infectivity. Highly pathogenic avian influenza viruses possess the multibasic cleavage site of the HA which is cleaved by ubiquitous proteases, such as furin; in contrast, the monobasic HA motif is recognized and activated by trypsin-like proteases, such as the transmembrane serine protease 2 (TMPRSS2). Here, we aimed to determine the effects of TMPRSS2 on the replication of pandemic H1N1 and H3N2 subtype IAVs in the natural host, the pig. The use of the CRISPR/Cas 9 system led to the establishment of homozygous …