Biochemistry, Biophysics, and Structural Biology Commons^™

Role And Regulation Of Sphingosine 1-Phosphate In Erythrocyte, Kaiqi Sun

Dissertations and Theses (Open Access)

Sphingosine 1-phosphate (S1P) is a bioactive signaling sphingolipid produced in every mammalian cell. It plays a variety of important roles both in and outside of cells. S1P is highly enriched in mature erythrocytes because of the high enzymatic activity of the S1P-generating enzyme Sphingosine Kinase 1 (Sphk1) and the absence of S1P degrading enzymes. Erythrocytes are considered only a major reservoir for S1P because they supply S1P to the circulation for the regulation of various physiological processes which include but are not limited to immune cell trafficking, endothelial integrity and hematopoietic stem cell mobilization. However, if S1P plays a role …

Fret-Based Investigations Of The Structure-Function Relationships In The Nmda Receptor, Drew M. Dolino

Dissertations and Theses (Open Access)

The N-methyl-D-aspartate (NMDA) receptor is one member of a class of proteins known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory neurotransmission in the central nervous system, with the NMDA receptor standing out among these receptors for its requirement of a co-agonist, its magnesium-block-based coincidence detection, its slow kinetics, its calcium permeability, its allosteric modulation, and its especially important functional roles in synaptic plasticity, excitotoxicity, and more. In recent years, a wealth of structural information has come about describing endpoint structures to high resolution, but such structures are unable to fully resolve the movements …

Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa

Dissertations and Theses (Open Access)

NON-CODING RNAS IDENTIFY THE INTRINSIC MOLECULAR SUBTYPES OF MUSCLE-INVASIVE BLADDER CANCER

Andrea Elizabeth Ochoa, B.S.

Advisory Professors: David J. McConkey, Ph.D. and Joya Chandra, Ph.D.

There has been a recent explosion of genomics data in muscle-invasive bladder cancer (MIBC) to better understand the underlying biology of the disease that leads to the high amount of heterogeneity that is seen clinically. These studies have identified relatively stable intrinsic molecular subtypes of MIBC that show similarities to the basal and luminal subtypes of breast cancer. However, previous studies have primarily focused on protein-coding genes or DNA mutations/alterations.

There is emerging evidence implicating …

Analysis Of The Biochemical And Cellular Activities Of Substrate Binding By The Molecular Chaperone Hsp110/Sse1, Veronica M. Garcia

Dissertations and Theses (Open Access)

Molecular chaperones ensure protein quality during protein synthesis, delivery, damage repair, and degradation. The ubiquitous and highly conserved molecular chaperone 70-kDa heat-shock proteins (Hsp70s) are essential in maintaining protein homeostasis by cycling through high and low affinity binding of unfolded protein clients to facilitate folding. The Hsp110 class of chaperones are divergent relatives of Hsp70 that are extremely effective in preventing protein aggregation but lack the hallmark folding activity seen in Hsp70s. Hsp110s serve as Hsp70 nucleotide exchange factors (NEF) that facilitate the Hsp70 folding cycle by inducing release of protein substrate from Hsp70, thus recycling the chaperone for a …

The Role Of Adenosine Signaling In Mature Erythrocytes And Erythroid Progenitors, Hong Liu

Dissertations and Theses (Open Access)

Adenosine is a ubiquitous nucleoside in almost all the cells throughout our bodies. It is highly induced particularly under hypoxia or energy depletion conditions. Adenosine functions as a critical ligand, after binding to membrane-associated adenosine receptors, adenosine initiates a downstream signaling cascade and subsequently contributes to functions of nervous system, immune response, vascular function and even metabolism.

Hypoxia is a condition with limited O₂ availability in the whole body or a region of the body. It is a major consequence of many respiratory and cardiovascular diseases, as well as for people living and working at high altitudes or other …

Understanding The Mechanism Of Genomic Instability During Replicative Aging In Budding Yeast, Sangita Pal

Dissertations and Theses (Open Access)

Aging brings a gradual decline in molecular fidelity and biological functionality, resulting in age related phenotypes and diseases. Despite continued efforts to uncover the conserved aging pathways among eukaryotes, exact molecular causes of aging are still poorly understood. One of the most important hallmarks of aging is increased genomic instability. However, there remains much ambiguity as to the cause. I am studying the replicative life span (RLS) of the genetically tractable model organism Saccharomyces cerevisiae, or budding yeast using the innovative “mother enrichment program” as the method to isolate unparalleled numbers of aged yeast cells to investigate the molecular changes …

Influence Of Histidine Residues, Ph And Charge Interactions On Membrane-Spanning Peptides, Ashley N. Henderson

Graduate Theses and Dissertations

Designed transmembrane peptides were employed for investigations of histidine residues within the hydrophobic environment of the lipid bilayer by means of oriented solid-state deuterium NMR spectroscopy. Using the model peptide GWALP23 sequence (GGALW(LA)6LWLAGA) as a host framework, the effects of single and double histidine mutations were explored. Replacement of leucine residue 12 to polar neutral histidine had little influence on the peptide average orientation, however under strongly acidic pH conditions in DOPC bilayers, the histidine becomes positively charged (pKa 2.5) and the GWALP23-H12 peptide exits the membrane and adopts a surface-bound orientation. Conversely, mutation of leucine 14 to neutral histidine …

Identification Of Molecular Signatures Of Environmental And Nutritional Stress Responses In Poultry, Phuong Hieu Nguyen

Graduate Theses and Dissertations

Poultry production plays an important role in the food supply and security for billions of people. Poultry meat is considered the most efficient, nutritious source of protein, without religious taboos, and is relatively inexpensive. However, the poultry industry is facing substantial challenges. The global environmental temperature has experienced dramatic changes in the last few years. Modern broilers are not well adapted to environmental challenges (heat and cold stress), which have resulted in heavy economic loss in the poultry industry worldwide. In addition, the use of feed restriction regimens in management of breeders as well as the transportation of young chicks …

A Genetic Analysis Of Nuclear Functions Of The Lipin Protein In Drosophila Melanogaster, Xeniya Rudolf

Graduate Theses and Dissertations

Lipins are a family of proteins that have critical functions in the control of fat storage and energy homeostasis. Biochemically, lipins have two functions. They provide an enzymatic activity (phosphatidate phosphatase or PAP activity) in the glycerol-3 phosphate pathway that leads to the production of storage fats (triacylglycerols). In addition, they play a role in the regulation of genes in the cell nucleus as transcriptional co-regulators. The PAP activity of lipins has been widely studied in a number of organisms. However, the transcriptional co-regulator function is not as well described in the literature. The transcriptional function of lipins depends on …

Science, Between The Lines: Rosalind Franklin, Rachael Renzi

Senior Honors Projects

The purpose of this paper is to contrast scientific rhetoric with creative biographical writing style. Both forms of communication rely on specific syntax and styles to describe research findings to the appropriate audiences, but the often passive format of scientific literature excludes the passionate reasonings of the researcher. In order to understand why the scientist is kept separate from his or her published findings, I am going to experiment with the two contrasting forms. Throughout the paper, each form will be tested and used at varying levels. Both scientific and creative writing will be mixed. To emphasize the technically dense …

Using Rb-Tnseq To Analyze Natural Variation In Saccharomyces Cerevisiae, Syed Raza Mahmood

Graduate Theses and Dissertations

One of the main challenges in biology today is the characterization of millions of genes of unknown function being continuously identified in sequencing studies. Transposon mutagenesis is a technique that has been widely used for annotating gene function and has now been combined with next-generation sequencing (Tn-Seq) to assess mutant fitness on a genome wide basis. However, Tn-Seq approaches are often constrained by laborious library preparation protocols which limit the number of organisms or conditions that can be assessed. Random bar code transposon-site sequencing (RB-TnSeq), is a transposon sequencing technique that streamlines library preparation and increases the throughput of mutant …

Thylakoid Protein Targeting/Insertion By A Signal Recognition Particle In Chloroplasts, Priyanka Sharma

Graduate Theses and Dissertations

Protein targeting is a fundamental cellular process that directs proteins from their site of synthesis to the site where they function. The signal recognition particle (SRP) dependent targeting pathway is conserved in both eukaryotes and prokaryotes where it co-translationally targets polypeptide chains emerging from ribosomes to the endoplasmic reticulum (eukaryotes) or cytoplasmic membrane (prokaryotes). A structurally unique form of SRP is found in chloroplasts where it functions to post-translationally bind and target a subset of integral thylakoid membrane proteins, the light harvesting chlorophyll binding proteins (LHCPs). Mature LHCPs bind chlorophyll a/b and function in photosynthetic light capture. Like many other …

Conservative Tryptophan Mutations In Protein Tyrosine Phosphatase Ptp1b And Its Effect On Catalytic Rate And Chemical Reaction, Teisha Richan

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Protein-tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphorylated tyrosines by a 2-step mechanism involving nucleophilic attack by cysteine and general acid catalysis by aspartic acid. In most PTPs the aspartic acid resides on a flexible protein loop, consisting of about a dozen residues, called the WPD loop. PTP catalysis rates span several orders of magnitude, and differences in WPD loop dynamics have recently been show to correlate with the rate of enzymatic catalysis. The rate of WPD loop motion could possibly be related to a widely conserved tryptophan residue on the WPD loop. Therefore, point mutants were made in PTP1B …

Mechanism Of Substrate Reduction By Nitrogenase, Nimesh Khadka

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Nitrogen (N) is a vital element of life and the main component of chemical fertilizer. The industrial Haber-Bosch process fulfills the demands of today’s nitrogen need and is therefore considered as one of the major scientific breakthroughs of the last century. However, the Haber-Bosch process operates at very high temperature and pressure, and requires fossils fuels to drive the reaction, making it an energy expensive process. The energy demand for this process accounts for almost 3% of the total global energy consumption. In addition, the rapid population growth, economic development and depletion of limited non-renewable fossil fuels have already created …

First-Row Transition Metal Sulfides And Phosphides As Competent Electrocatalysts For Water Splitting, Nan Jiang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Solar energy is a carbon-neutral and renewable energy resource. Its nature of intermittence and unequal distribution requires efficient solar energy capture, conversion, and storage. Solar-driven water splitting to produce hydrogen and oxygen is widely considered as an appealing approach to meet this goal, in which hydrogen acts as a green energy carrier. Water splitting consists of two redox half reactions: hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Both reactions involve the transfer of multiple electrons and protons and possess high energy barriers to proceed at appreciable rates, hence catalysts are needed.

A large number of HER and OER …

The Effect Of Galactose On The Expression Of Genes Regulated By Rrp6p, Mary Megan Pelkowski, Kevin Callahan

The Review: A Journal of Undergraduate Student Research

Gene expression is a multi-faceted phenomenon, governed not only by the sequence of nucleotides, but also by the extent to which a particular gene gets transcribed, how the transcript is processed, and whether or not the transcript ever makes it out of the nucleus. Rrp6p is a 5’-3’ exonuclease that can function independently and as part of the nuclear exosome in Saccharomyces cerevisiae (Portin, 2014). It degrades various types of aberrant RNA species including small nuclear RNAs, small nucleolar RNAs, telomerase RNA, unspliced RNAs, and RNAs that have not been properly packaged for export (Butler & Mitchell, 2010). This exosome …

Sickle Cell Anemia: Current Treatments And Potential Advancements, Vanessa Martinez

Selected Honors Theses

Sickle cell anemia is a disease that affects red blood cells, specifically the hemoglobin protein. An amino acid mutation in the gene that encodes β-globin leads to malformation of the β subunit of hemoglobin.3, Valine becomes glutamic acid in the mutated β-globin gene.9 The mutation malformation leads to the red blood cells becoming sickle shaped, or crescent shaped.3,4 The sickle shape of red blood cells in individuals with sickle cell disease leads to vaso-occlusive crisis.9 Vaso-occlusive crisis includes complications such as blood clotting, chronic pain, organ failure, organ death, and possibly early mortality.9 The Centers for Disease Control and Prevention …

Melatonin And Its Metabolites Protect Human Melanocytes Against Uvb-Induced Damage: Involvement Of Nrf2-Mediated Pathways, Zorica Janjetovic, Stuart G. Jarrett, Elizabeth F. Lee, Cory Duprey, Russel J. Reiter, Andrzej T. Slominski

Toxicology and Cancer Biology Faculty Publications

Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing …

Design Of A Robust Undergraduate Biochemistry Laboratory Course Based On A Modified And Expanded Bovine Serum Albumin Purification Scheme, Odutayo O. Odunuge, Nicholas Cheatwood, John Mullins, Michele Harris

Symposium on Arts and Research

The ASBMB curriculum for an undergraduate degree recommends a set of skills that can be acquired only through laboratory courses and research experience. Based on a previously reported purification scheme for BSA (Odunuga and Shazhko, 2013), we designed a robust, reproducible, cost-effective, safe and enquiry-based undergraduate biochemistry laboratory course that encompasses many of the skill-sets recommend-ed in the ASBMB curriculum. Our work not only modi-fied certain steps in the scheme, it also included addi-tional steps to enhance student learning and skill ac-quisition. Salt precipitation, ion exchange and size ex-clusion chromatography were employed by students to purify BSA from cow plasma. …

Determining The Effects Of Palmitoylation On Rho Family Gtpase Tcl Gtp Binding Activity Using Palmitoyl Co-A, Grace Young

Honors Capstones

Capstone submitted as a graduation requirement for BSU Honors Program.

Relative Importance Of Black Carbon, Brown Carbon, And Absorption Enhancement From Clear Coatings In Biomass Burning Emissions, Rudra P. Pokhrel, Eric R. Beamesderfer, Nick L. Wagner, Justin M. Langridge, Daniel A. Lack, Thilina Jayarathne, Elizabeth A. Stone, Chelsea E. Stockwell, Robert J. Yokelson, Shane M. Murphy

Chemistry and Biochemistry Faculty Publications

A wide range of globally significant biomass fuels were burned during the fourth Fire Lab at Missoula Experiment (FLAME-4). A multi-channel photoacoustic absorption spectrometer (PAS) measured dry absorption at 405, 532, and 660 nm and thermally denuded (250 °C) absorption at 405 and 660 nm. Absorption coefficients were broken into contributions from black carbon (BC), brown carbon (BrC), and lensing following three different methodologies, with one extreme being a method that assumes the thermal denuder effectively removes organics and the other extreme being a method based on the assumption that black carbon (BC) has an Ångström exponent of unity. The …

Antimicrobial Properties Of S-Benzofuran-2-Yl Ethanol Produced By Biotransformation, Nick Cheatwood, Ann Davis, Elizabeth Schabeck, Kelsi Hooker, Michele Harris

Undergraduate Research Conference

All living organisms contain enzymes to carry out biological reactions, which produce substances with a specific three dimensional shape. Enantiomers are two molecules that are mirror images of each other just as hands are mirror images of each other. It is well known in the pharmaceutical world that one of the enantiomers (one of the mirrorimage molecules) has a positive biological effect while the other can be harmful or have no effect. Currently, any potential pharmaceutical that could exist as enantiomers must have each enantiomer tested for biological activity prior to FDA approval. In our laboratory, we have focused on …

Dna-Binding And Cellular Uptake Properties Of Pyrrole-Imidazole Polyamides, Maria J. Scuderi

Dissertations

Pyrrole-imidazole polyamides (PAs) represent a class of synthetic ligands that bind to the minor groove of DNA through hydrogen bonds and can be programmed to recognize predetermined DNA sequences. Potential applications of these compounds include gene expression modulation, antimicrobial activity and cell imaging.

Studies conducted in our lab in collaboration with NanoVir have shown that large PAs exhibit antiviral activity against Human Papillomavirus (HPV), which is the most common sexually transmitted infectious agent in the US and the primary factor for the development of cervical cancer. PAs act against HPV by targeting the viral DNA and promoting its selective elimination …

Physiological Effects Of Five Different Marine Natural Organic Matters (Noms) And Three Different Metals (Cu, Pb, Zn) On Early Life Stages Of The Blue Mussel (Mytilus Galloprovincialis), Lygia Sega Nogueira, Adalto Bianchini, Scott Smith, Marianna Basso Jorge, Rachael L. Diamond, Chris M. Wood

Chemistry Faculty Publications

Metals are present in aquatic environments as a result of natural and anthropogenic inputs, and may induce toxicity to organisms. One of the main factors that influence this toxicity in fresh water is natural organic matter (NOM) but all NOMs are not the same in this regard. In sea water, possible protection by marine NOMs is not well understood. Thus, our study isolated marine NOMs by solid-phase extraction from five different sites and characterized them by excitation-emission fluorescence analysis—one inshore (terrigenous origin), two offshore (autochthonous origin), and two intermediate in composition (indicative of a mixed origin). The physiological effects of …

Biophysical Studies Of Hairpin Polyamides With Broad-Spectrum Activity Against High-Risk Human Papillomaviruses, Carlos H. Castaneda

Dissertations

Human papillomavirus is a small dsDNA virus that infects mucosal and cutaneous epithelial tissues. Persistent infection with high-risk HPV is the main etiological agent in the development of cervical cancer worldwide. Although prophylactic vaccines against HPV are available, these preventative measures are type-specific and are ineffective against existing infections. Thus, there is a pressing need for antiviral drugs with a broad-spectrum activity against HPV to eradicate existing infections, no matter the subtype.

Our group and collaborators have synthesized an extensive library of novel N-methylpyrrole/N-methylimidazole (Py/Im) hairpin polyamides (PAs) with broad-spectrum activities against three prevalent oncogenic-HPV types (HPV16, …

With Or Without Nutrients, Sponges Are Boring: The Effects Of Eutrophication On Bioerosion, Amber D. Stubler, John M. Carroll, Christopher M. Finelli

Biology: Faculty Presentations

Eutrophication, largely due to coastal development and human activities, is an ongoing issue for coastal ecosystems. Excess nutrients can impact ecosystem processes, promote the occurrence of algal blooms, and decrease the overall water quality. One process that may be impacted by eutrophication is the biological breakdown of carbonate material, or bioerosion. Correlative evidence suggests that bioeroding sponges increase in size and abundance along nutrient gradients, leading to increased bioerosion rates. However, there have been no experimental studies investigating the direct effects of increased nutrients on sponge bioerosion rates. To determine whether sponge bioerosion of carbonate material is enhanced under eutrophied …

Bay Scallops: The High Resolution Canary In The Highly-Fertilized Coal Mine, Jessica L. Carlton, Lorie E. Williams, John M. Carroll, Steve T. Tettelbach, Bradley J. Peterson, Aswani K. Volety, Elizabeth S. Darrow

Biology: Faculty Presentations

As human populations increase in watersheds, the Peconic Bay estuary (NY) has experienced increased nitrogen (N) loads, resulting in eutrophication. Stable isotopes can be used as indicators of anthropogenic N sources such as wastewater and fertilizer, and potentially be used to track source-specific N inputs through time. We hypothesized that Peconic Bay scallops (Argopecten irridians) could be proxies for these environmental changes through assimilation of organic matter from surrounding water into their soft tissue and shells. We examined nitrogen stable isotopes (δ¹⁵N) from whole soft tissue and shell of scallops collected throughout the Peconic. A strong correlation was …

Not A Fun Threesome: The Prevalence, Impact And Interaction Of Boring Sponges And Pea Crabs On Oysters, John M. Carroll, Jessica C. Watts, Christopher M. Finelli, Daphne Munroe

Biology: Faculty Presentations

The eastern oyster, Crassostrea virginica, provides a number of ecosystem services and is an important commercial fishery species along US East and Gulf Coasts. Unfortunately, their populations have declined dramatically, due to overharvest, habitat loss, and disease. As both oyster restoration efforts and aquaculture of oysters continues to increase throughout their range, it is important to consider the impacts of a number of potential oyster pests, including the boring sponge Cliona spp. and the pea crab Zaops (Pinnotheres) ostreum on oyster populations. Both of these pests have been demonstrated to reduce oyster growth, condition, and in some instances, reproductive output. …

Restoration By Transplantation: Using A Filter-Feeding Gastropod, Crepidula Fornicata, To Rehabilitate Great South Bay, New York: Preliminary Surveys, Nicole L. Kleinas, Bradley J. Peterson, Stephen T. Tettelbach, John M. Carroll

Biology: Faculty Presentations

Coastal biogenic habitats provide a plethora of ecosystem services that enhance the commercial and recreational value of the system. Specifically, shellfish beds play a critical role in improving water quality, creating complex habitat for other commercial species, and serving as a trophic resource for surrounding nutrient-poor habitats. Great South Bay, New York, was historically one of the most productive estuaries in the nation, yet commercial shellfisheries have collapsed here due to overharvest. These filter-feeding shellfish species, in particular hard clams Mercenaria mercenaria, once provided important ecosystem services, including top-down control of phytoplankton blooms. Overharvest of clams has led to …

Determining The Role Of The N- And C- Terminin In Localizing Tcl.Rhoj To Cellular Membranes, Brooke Tader

Honors Capstones

Capstone submitted as a graduation requirement for BSU Honors Program