Biochemistry, Biophysics, and Structural Biology Commons^™

Enhancing Therapeutic Approaches For Melanoma Patients Targeting Epigenetic Modifiers., Maria Gracia-Hernandez, Zuleima Munoz, Alejandro Villagra

Biochemistry and Molecular Medicine Faculty Publications

Melanoma is the least common but deadliest type of skin cancer. Melanomagenesis is driven by a series of mutations and epigenetic alterations in oncogenes and tumor suppressor genes that allow melanomas to grow, evolve, and metastasize. Epigenetic alterations can also lead to immune evasion and development of resistance to therapies. Although the standard of care for melanoma patients includes surgery, targeted therapies, and immune checkpoint blockade, other therapeutic approaches like radiation therapy, chemotherapy, and immune cell-based therapies are used for patients with advanced disease or unresponsive to the conventional first-line therapies. Targeted therapies such as the use of BRAF and …

Discovery Of Phosphotyrosine-Binding Oligopeptides With Supramolecular Target Selectivity, Ana S. Pina, Leonor Morgado, Krystyna L. Duncan, Sara Carvalho, Henrique F. Carvalho, Armenio J. M. Barbosa, Beatriz De P. Mariz, Ines P. Moreira, Daniela Kalafatovic, Bruno M. Morais Faustino, Vishal Narang, Tong Wang, Charalampos G. Pappas, Isabel Ferreira, A. Cecılia A. Roque, Rein V. Ulijn

Advanced Science Research Center

We demonstrate phage-display screening on self-assembled ligands that enables the identification of oligopeptides that selectively bind dynamic supramolecular targets over their unassembled counterparts. The concept is demonstrated through panning of a phage-display oligopeptide library against supramolecular tyrosine-phosphate ligands using 9-fluorenylmethoxycarbonyl-phenylalanine-tyrosine-phosphate (Fmoc-FpY) micellar aggregates as targets. The 14 selected peptides showed no sequence consensus but were enriched in cationic and proline residues. The lead peptide, KVYFSIPWRVPM-NH2 (P7) was found to bind to the Fmoc-FpY ligand exclusively in its self-assembled state with KD = 74 ± 3 μM. Circular dichroism, NMR and molecular dynamics simulations revealed that the peptide interacts with Fmoc-FpY …

The Application Of Mathematical Optimization And Flavor-Detection Technologies For Modeling Aroma Of Hops, Yutong Liu

Department of Food Science and Technology: Dissertations, Theses, and Student Research

In recent years, proprietary hops (Citra, Simcoe, and Mosaic) become the most sought-after hops among brewers due to their excellent aroma. However, they are restricted to the owners unless other growers purchase the costly licensing agreements. Many public hops are available to the growers without any additional costs, but their aroma is difficult to match to the proprietary hops. Although proprietary and public hop varieties are unique in their aroma profiles, all hops varieties contain similar volatile compounds, merely differ in the quantity of different individual compounds. The main objective of this thesis was to investigate the feasibility of matching …

A Temporal Analysis Of The Microbiota And Biofouling Development On Artificial Substrates In The Port Everglades Inlet, Florida, Denise Swack

All HCAS Student Capstones, Theses, and Dissertations

A pilot project was deployed in Port Everglades Inlet, Florida that aimed to evaluate the biofilm composing the microbiome on ecologically engineered artificial substrates used to build Coastal Marine Infrastructure. In April of 2017, an Articulated Concrete Block Mattress comprised of an ecological engineered concrete substrate and a standard smooth surface control substrates were compared. This study will provide a profile on the microbiome community on artificial substrates within Port Everglades Inlet on bio-enhancing concrete-based solutions in our Coastal Marine Infrastructure. To study the microbial community, the 16s rRNA technology was used in Illumina’s high-throughput DNA sequencing. Samples were collected …

Doors Pushed Open: For Devin Gibbs, College Seemed Like A Longshot--Until It Wasn't, Kardelen Koldas

Colby Magazine

Before enrolling, Devin Gibbs ’14 received an invitation from Colby. The letter offered to bring him to campus and provide accommodations so he could get a feel for the school. What it didn’t say was he had, in essence, been admitted. Gibbs, who lived in Waterville just minutes from campus, thought the letter was a scam. “I had never gotten anything for free before,” he said.

Single-Variable Porous Nanomaterial Series From Polymer Structure-Directing Agents, Morgan Stefik

Faculty Publications

Block polymer structure-directing agents (SDA) enable the production of porous nanoscale materials. Most strategies rely upon polymer equilibration where diverse morphologies are realized in porous functional materials. This review details how solvent selectivity determines the polymer SDA behaviors, spanning from bulk-type to solution-type. Equilibrating behavior of either type, however, obscures nanostructure cause-and-effect since the resulting sample series convolve multiple spatial variations. Solution-type SDA behaviors include both dynamic and persistent micelles. Persistent micelle templates (PMT) use high solvent selectivity for kinetic entrapment. PMTs enable independent wall thickness control with demonstrated 2 Å precision alterations. Unimodal PMT pore size distributions have spanned …

Differentiating The Mechanistic Role And Chemotherapeutic Potential Of Src And Podoplanin In Oncogenic Transformation, Edward P. Retzbach

Graduate School of Biomedical Sciences Theses and Dissertations

There were an estimated 20 million new cancer cases worldwide in 2020, resulting in nearly 1000 deaths per hour [1]. Oral cancer exemplifies the difficulties of treating cancer patients. The first line for oral cancer treatment is surgery and radiation that can lead to patient disfigurement and decreased quality of life in cancer survivors [2-4]. Though there have been many developments in chemotherapy in the last 30 years, the 50% mortality rate associated with oral cancer has not changed [4, 5]. Longitudinal studies that track survival rates in oral cancer patients demonstrate a 3-fold reduction in patient deaths when patients …

Adrenocortical Attunement, Reactivity, And Potential Genetic Correlates Among Parent-Daughter Dyads From Low-Income Families, Jennifer Byrd-Craven, Michael M. Criss, Jessica L. Calvi, Lixian Cui, Amanda Baraldi, Amanda Sheffield Morris

Athletic Performance Research

Examining the multitude of influences on the development of adolescent stress responses, especially among low-income families, is a critical and understudied topic in the field. The current study examined cortisol attunement between adolescent girls and parents (mostly mothers) from predominantly low-income, single parent, ethnic minority families before and after an in-laboratory disagreement discussion task. The sample consisted of 118 adolescents (M_age = 13.79 years, 76.3% ethnic minorities, 23.7% European Americans) and primary caregivers (M_age = 40.62 years; Mdn yearly income = $24,000; 43.2% single parents; 50% living below poverty line). We investigated oxytocin receptor (OXTR rs53576) …

Computational And Biochemical Characterizations Of Anhydrobiosis-Related Intrinsically Disordered Proteins., Brett R. Janis

Electronic Theses and Dissertations

Anhydrobiosis is the remarkable phenomenon of “life without water”. It is a common technique found in plant seeds, and a rare technique utilized by some animals to temporarily stop the clock of life and enter a stasis for up to several millennia by removing all of their cellular water. If this phenomenon can be replicated, then biological and medical materials could be stored at ambient temperatures for centuries, which would address research challenges as well as enhance the availability of medicine in areas of the world where refrigeration, freezing, and cold-chain infrastructure are not developed or infeasible. Furthermore, modifying crop …

Charting A New Frontier Integrating Mathematical Modeling In Complex Biological Systems From Molecules To Ecosystems, Katharine A. White, Kira D. Mcentire, Nicole R. Buan, Lecia Robinson, Elisar Barbar

Department of Biochemistry: Faculty Publications

Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, and ecological) have transformed how we understand, categorize, and predict complex biological systems. This surge of quantitative data creates an opportunity to apply, develop, and evaluate mathematical models of biological systems and explore novel methods of analysis. Simultaneously, thanks to increased computational power, mathematicians, engineers, and physical scientists have developed sophisticated models of biological systems at different scales. Novel modeling schemes can offer deeper understanding of principles in biology, but there is still a disconnect between modeling and experimental biology that limits our ability to fully realize …

Molecular Mechanisms Underlying The Suppression Of Cardiomyocyte Necroptosis By The Cop9 Signalosome In Mice, Megan T. Lewno

Dissertations and Theses

Background: Within a large subset of heart failure, cardiac ubiquitin-proteasome system (UPS) inadequacy is causative. A vital UPS regulator is the COP9 signalosome (CSN). The CSN holocomplex is formed by 8 unique protein subunits (COPS1~COPS8) and regulates Cullin-RING ligases via Cullin deneddylation. Cardiomyocyte-restricted knockout (cko) of Cops8 causes massive cardiomyocyte necroptosis via the RIPK1-RIPK3-MLKL pathway, resulting in dilated cardiomyopathy (DCM) and shortened lifespan in mice. CSN’s deneddylase resides in COPS5 and Cops5-cko has not been explored. It is important to investigate how the necroptotic pathway within cardiomyocytes is activated in Cops8-cko mice as cardiomyocyte necroptosis has been shown to play …

College Of Natural Sciences Newsletter, December 2021, College Of Natural Sciences

College of Natural Sciences Newsletters and Reports

Volume 2, Issue 12

Page 1 Dean's Message
Page 2 Awards & Recognition
Page 2 Media Coverage of CNS
Page 3 Media Coverage Cont.
Page 4 Science as Art Competition
Page 5 Open PRAIRIE Data
Page 5 Grants Awarded in CNS

Spectroscopic Studies Of The Interaction Between Phosphorus Heterocycles And Cytochrome P450, Dumei Ma, Libo Zhang, Yingwu Yin, Yuxing Gao, Qian Wang

Faculty Publications

P450 fatty acid decarboxylase OleT from Staphylococcus aureus (OleT_SA) is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO₂ or minor α- and β-hydroxylated fatty acids as side-products. In this work, the interactions between a series of cycloalkyl phosphorus heterocycles (CPHs) and OleT_SA were investigated in detail by fluorescence titration experiment, ultraviolet–visible (UV–vis) and ³¹P NMR spectroscopies. Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6, a representative CPHs, interacted with OleT_SA with a binding constant value of 15.2 …

Modulation Of Rho Termination : Expectation Vs Reality, Kavya Sri Sai Chegireddy

Legacy Theses & Dissertations (2009 - 2024)

Transcription termination factor Rho is an essential protein in many bacteria. Rho is an ATP-dependent RNA helicase that accounts for 20-50% of termination events in Escherichia coli and plays an important role in preventing pervasive transcription that otherwise might be lethal to bacteria. Rho termination usually occurs in the 3’ UTRs and non-coding regions of the DNA, and the actively transcribing RNA is believed to be protected by translating ribosomes from Rho termination since both transcription and translation are a simultaneous process in prokaryotes. However, in reality, Rho terminates transcription of some protein-coding genes, and fails to terminate transcription of …

Lipidomic Analysis Of Various Developmental Stages Of Physcomitrium Patens, Deepshila Gautam

Electronic Theses and Dissertations

Lipids maintain fluidity of the cell membrane during the lifetime of all organisms. The moss Physcomitrium patens, an early land plant, enters reproductive phase under cold (15°C) conditions relative to its gametophytes (22°C). Thus, we hypothesized that their lipid content and composition would be distinct. Using ESI-MS/MS, we showed that the content and acyl composition of 11 lipid classes varied during development. Galactolipids were abundant in gametophytes but insignificant in sporophytes; among phospholipids, phosphatidylcholine was predominant in both phases. Although, sporophytes contained around five-fold less lipids than the gametophyte, their phosphatidic acid content, which accumulates during stress, was 18-fold …

Expanding The Conservation Genomics Toolbox: Incorporating Structural Variants To Enhance Genomic Studies For Species Of Conservation Concern, Stephanie J. Galla

Biology Faculty Publications and Presentations

Structural variants (SVs) are large rearrangements (>50 bp) within the genome that impact gene function and the content and structure of chromosomes. As a result, SVs are a significant source of functional genomic variation, that is, variation at genomic regions underpinning phenotype differences, that can have large effects on individual and population fitness. While there are increasing opportunities to investigate functional genomic variation in threatened species via single nucleotide polymorphism (SNP) data sets, SVs remain understudied despite their potential influence on fitness traits of conservation interest. In this future-focused Opinion, we contend that characterizing SVs offers the conservation genomics …

Expression And Purification Of Cytochrome 2u1 And Canine 1a2 And Metabolism Of Caffeine By Cytochrome 1a2, Brenda M. Wekesa

Graduate Theses/Dissertations

Cytochrome P450 enzymes are a large family of membrane heme proteins involved in eliminating drugs and the synthesis or elimination of steroids, eicosanoids, and vitamins. CYP2U1 is one of the poorly characterized P450 enzymes classified as orphan cytochrome P450 with unknown exact biological function. It is expressed in the brain and thymus as a catalyst in the hydroxylation of arachidonic acid. Unlike other cytochrome P450s, CYP2U1 is a bit unusual with forty extra amino acids. If a mutation occurs, it can lead to an early onset inherited disorder of the central nervous system called Hereditary Spastic Paraplegias (HSP). Most of …

Engineering Fluorescently Labeled Human Fibroblast Growth Factor One Mutants And Characterizing Their Photophysics Properties Towards Designing Fret Assays, Mamello Mohale

Graduate Theses and Dissertations

Human fibroblast growth factor one (hFGF1) belongs to a family of 22 FGF members produced by fibroblast cells. Cell signaling during physiological processes of angiogenesis and wound healing occurs when hFGF1 binds to its receptor (FGFR). However, when heterogenous homeostasis is not maintained, fibroblast cells exhibit excessive proliferation which can lead to a myriad of cancers. smFRET is an ultrasensitive distant dependent (1-10 nm) technique capable of resolving such heterogeneity in structural dynamics and binding affinities (Kd). Therefore, we successfully designed and characterized fluorescently labeled hFGF1 tracers which span the visible light region of the electromagnetic spectrum for use in …

Characterization Of The Multifunctional Enzyme Proline Utilization A, Yizi Mao

Department of Biochemistry: Dissertations, Theses, and Student Research

Proline is a unique and important amino acid. Proline is a proteogenic amino acid and its metabolism is involved in many critical cellular functions. Therefore, proline metabolism is tightly regulated, and dysfunction of proline metabolism is related to human diseases. The first step of proline oxidization to ∆¹-pyrroline-5-carboxylic acid (P5C) is catalyzed by proline dehydrogenase (PRODH). P5C is then non-enzymatically hydrolyzed to glutamate-γ-semialdehyde (GSA), which can be further oxidized to glutamate by P5C dehydrogenase (P5CDH/GSALDH). In Gram-negative bacteria, the PRODH and P5CDH enzymes are expressed as one polypeptide called proline utilization A (PutA). In some Gram-negative bacteria an …

V-Myb Avian Myel Oblast Viral Oncogene Homolog Like 1 (Mybl1) Knockdown And Its Role In A Triple Negative Breast Cancer, Nabras Mahmoud Abdulrahman

Theses (2016-Present)

Triple Negative Breast Cancer (TNBC) is defined as negative for three genes, estrogen receptor (ESR), progesterone receptor (PR) and Human epidermal growth factor receptor (HER2-neu) genes. Previous data show the V-Myb Avian Myel oblast Viral Oncogene Homolog Like 1 (MYBL1) gene is over-expressed in Triple negative breast cancer cell line (MDA-MB231). MYBL1 belongs to the MYB family of genes which are transcription factors and proto-oncogenes which are associated with cell cycle regulation, apoptosis, and differentiation, all of which are key events associated with cancers. It could be that MYBL1 contributes to these same processes in TNBC. Instead of studying MYBL1’s …

Mechanisms For Extracellular Matrix-Dependent Blood-Brain Barrier Dysfunction, Brian Adam Hoettels

Boise State University Theses and Dissertations

Dysfunction of the blood vessels that form the blood-brain barrier (BBB) is observed across various neurological disorders, including multiple sclerosis (MS). As barrier loss culminates in neuronal dysfunction and degeneration, a better understanding of the mechanisms underlying BBB dysfunction is needed.

Tight junctions are multiprotein complexes maintained by the endothelial cells lining the inner blood vessel wall to seal the intercellular space, and their disruption impairs BBB function. In my first chapter, I focus on how tight junctions are altered in CNS inflammatory demyelinating diseases (CNS-IDDs) like MS as BBB dysfunction is one of the earliest known stages in …

Liposomes: Production And Applications For Controlled Drug Delivery, Gamid Abatchev

Boise State University Theses and Dissertations

This dissertation recognizes the enormous potential presented by the ever-evolving development of liposomes as drug carriers and seeks to offer further investigation into their useful production and utilization. The first chapter presents the basic principles governing their formation by self-assembly in water solutions, briefly describes the most common production methods, and points out essential past advances that led to their use as drug carriers. Chapter two exemplifies production of liposomes by the traditional methods of extrusion and sonication, detailing passive and active loading, as well as physical characterization by Dynamic Light Scattering, microscopy imaging, and fluorescence spectroscopy. In the next …

Enzymatic Degradation Of Microcystin-Lr By Microcystinase (Mlra), Faisal Alqhtani

Graduate Theses and Dissertations

Microcystin-LR (MC-LR) is affecting the water supply worldwide. Hence, a way to eliminate this toxin is an essential target. In this study, successful cloning of the mlrA gene and producing MlrA enzyme that can degrade the cyclic MC-LR to linearized MC-LR was done. MlrA protein was expressed in Escherichia coli BL-21 (E. coli). Also, enhancing the MlrA yield by adding nickel to LB media was a success in producing more MlrA enzyme from the same volume. Even though the enzyme showed no activity after adding Ni, the enzyme was expressed at a higher yield. Furthermore, it was to investigate adding …

Characterization Of Biomarkers For Alzheimer’S Disease And Hiv-1 Associated Neurocognitive Disorders, Armando Garces Iii

Theses and Dissertations

Alzheimer’s disease is a neurodegenerative disorder that is characterized by progressive cognitive decline and the accumulation of amyloid beta and neurofibrillary tangles in regions of the brain. These protein deposits are known to generate multiple effects on the brain that lead to neurodegeneration. It has been established that (Human Immunodeficiency Virus) HIV-1 accelerates the aging process of people living with HIV-1. Moreover, there is significant clinical evidence indicating a potential link between the neurodegeneration developed by those with an HIV-1 infection and AD. HIV-1 viral infection causes cognitive impairment known as …

Role Of The Nuclear Envelope In The Mechanoregulation Adipogenesis, Matthew H. Goelzer

Boise State University Theses and Dissertations

Mechanical signals are known regulators of mesenchymal stem cell (MSC) fate, regulating their differentiation into osteoblasts, chondrocytes, and adipocytes. These relevant mechanical signals reach to nucleus through nuclear envelope proteins such as Lamin A/C and the Linker of the Nucleoskeleton and Cytoskeleton (LINC) complexes. Within the context of bone, clinically relevant mutations of Lamin A/C and the LINC complexes have been shown to alter adipogenic and osteogenic MSC differentiation patterns, suggesting that that nucleo-cytoskeletal connectivity provided by nuclear envelope is important in regulating MSC fate. Using MSC adipogenesis as a model of MSC mechanical regulation, the goal of this work …

Evolutionary Development Study Of Firebrat (Thermobia Domestica), Luis Cantu Jr.

Theses and Dissertations

As most evolutionary development studies regarding wing origin take place using insects taxonomically closer to model organism, Drosophila melanogaster, there is a need of expanding studies to lower clades. While D. melanogaster is higher phylogenetically, basal clades would allow for a historical perspective of what occurs within the gene flow of conservative biomarkers. Further understanding of wings and flight would allow for a clearer understanding of how the migration of insects from sea to land has allowed them to become one of the most speciose taxa. Through the study of Thermobia Domestica, part of the Zygentoma, we expand on comprehension …

Development Of A Novel Strategy To Improve Checkpoint Immune Response In Pancreatic Cancer, Poornima Devi Shaji

Theses and Dissertations

Pancreatic Cancer is the 3rd lethal causing cancers in United States with a survival rate less than 5-7%. In advanced unresectable pancreatic cancer, treatment options are restrained to surgery because of its extreme aggressiveness. Immunotherapy, one of the current advanced treatments has shown promising response in other cancers. However, this therapy is limited in pancreatic cancer due to desmoplasia and fibrotic tumor microenvironment (TME).

Our superparamagnetic iron oxide nanoparticles (SPIONS) of curcumin (Curcuma longa, principal curcuminoid of turmeric) have potential ability to inhibit desmoplasia and tumor stroma with an increased bioavailability. This would soften up the tumors for …

The Role Of The Erbb Signaling Pathway In Cardiovascular Progenitor Cell-Based Repair, Christopher Ramos

Electronic Theses, Projects, and Dissertations

Adult mammalian hearts lack self-renewal and proliferative capabilities necessary for cardiovascular regeneration. Current treatments using cardiac progenitor cells (CPCs) for cell-based repair do not restore cardiac function in patients who experience a myocardial infarction (MI). Our laboratory has been studying Islet-1+ neonatal CPCs as a promising candidate for cell-based repair due to their ability to significantly improve cardiac function after MI in sheep. The current study addresses the hypothesis that the ERBB pathway is linked to the Hippo-pathway to activate YAP1 by the involvement of an autocrine loop that upregulates neuregulin (NRG). In our sheep model of MI and cardiovascular …

Reintegrating Biology Through The Nexus Of Energy, Information, And Matter, Kim L. Hoke, Sara L. Zimmer, Adam B. Roddy, Mary Jo Ondrechen, Craig E. Williamson, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Information, energy, and matter are fundamental properties of all levels of biological organization, and life emerges from the continuous flux of matter, energy, and information. This perspective piece defines and explains each of the three pillars of this nexus. We propose that a quantitative characterization of the complex interconversions between matter, energy, and information that compose this nexus will help us derive biological insights that connect phenomena across different levels of biological organization. We articulate examples from multiple biological scales that highlight how this nexus approach leads to a more complete understanding of the biological system. Metrics of energy, information, …

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …