Genetics and Genomics Commons^™

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Tactical Adjustment Of Signaling Leads To Increased Mating Success And Survival, Laura Sullivan-Beckers, Eileen A. Hebets

Eileen Hebets Publications

Most sexually reproducing animals overcome the challenge of searching for and attracting mates by utilizing signals that are broadcast through a spatially and temporally varying environment. A diverse suite of behavioral solutions exist for overcoming such environmental variability, including the adjustment of signaling behavior based upon receiver feedback. Few studies have directly examined the relationship between such tactical signaling adjustments and proxies of male fitness; the few that have, failed to find a relationship. Using the wolf spider, Schizocosa rovneri, we set out to first quantify among-male variation in the form and degree of responsiveness to female feedback. Following …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations and Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, [email protected] K. Busiek

Dissertations and Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and …

P53 Maintains Hepatic Cell Identity During Liver Regeneration, Zeynep Hande Coban Akdemir

Dissertations and Theses (Open Access)

p53 MAINTAINS HEPATIC CELL IDENTITY DURING LIVER REGENERATION

Zeynep Hande Coban Akdemir, B.S.,M.A.

Advisory Professor: Michelle Craig Barton, Ph.D.

p53 is a tumor suppressor that has been well studied in tumor-derived, cultured cells. However, its functions in normal proliferating cells and tissues are generally overlooked. We propose that p53 functions during the G1-S transition can be studied in normal, differentiated cells during surgery-induced liver regeneration. Two-thirds partial hepatectomy (PH) of mouse liver offers a unique model to compare p53 functions in regenerating versus sham (control) cells. My hypothesis is that intersection of global expression analyses (microarray and RNA sequencing) and …

Investigations Into Sensory Ecology And Gene Evolution Of The Pea Aphid (Acyrthosiphon Pisum), Swapna R. Purandare

School of Biological Sciences: Dissertations, Theses, and Student Research

Organisms use environmental cues to gather information required to perform activities that are essential for their survival and reproduction, such as searching for food, avoiding danger, and finding mates. They respond to the acquired information by changing their behavior or physiology, which may result in increased fitness. Due to the fundamental importance of information in an organism’s life, it is important to understand its acquisition, processing, and the organism’s response to it. In the work presented here, we used the pea aphid (Acyrthosiphon pisum), an insect that produces multiple phenotypes, or morphs, that are genetically identical, but differ …

The Mechanism Of Small Rna Biogenesis, Degradation, And Function In Arabidopsis, Meng Xie

School of Biological Sciences: Dissertations, Theses, and Student Research

Eukaryotic small RNAs play important roles in many biological processes through sequence-specific RNA silencing. In plants, there are mainly two small RNAs triggering gene silencing: microRNAs (miRNAs) and small interfering RNAs (siRNAs). The biogenesis and precise regulation of small RNA abundance are crucial for plant growth, development, genomic stability, and the resistance to both abiotic and biotic stresses. In this study, we used Arabidopsis thaliana, the model plant, to study the mechanism of RNA-directed DNA methylation (RdDM), in which siRNAs can trigger DNA methylation and gene silencing. In addition, we investigated the mechanism of miRNA biogenesis and degradation. For …

Clpxp Modulates Cell Growth And Morphology In Cell Shape Mutants Of E.Coli, Ryann Murphy

Senior Honors Projects

ClpXP modulates cell growth and morphology in cell shape mutants of E. coli

Ryann Murphy¹ and Jodi L. Camberg¹

¹University of Rhode Island, Department of Cell and Molecular Biology, Kingston, RI, 02881

Penicillin Binding Proteins (PBPs) are a family of prokaryotic membrane proteins named for their propensity to bind the antibiotic penicillin and are involved in remodeling and deposition of peptidoglycan. In wild type Escherichia coli cells, the uniform rod shape is conserved across generations. E.coli cells containing multiple deletions of Low Molecular Weight (LMW) PBPs exhibit irregular shapes. LMW PBP5 (dacA) is a potential …

Teaching Gene Regulation In The High School Classroom, Ap Biology,, Stefanie H. Baker, Marie Fox, Leigh Smith

Arthur Vining Davis High Impact Fellows Projects

This project sought to enhance high school students’ understanding of gene regulation as taught in an Advanced Placement Biology course. We accomplished this by designing and implementing a lab module that included a pre-lab assessment, a hands-on classroom experiment, and a post-lab assessment in the form of a lab poster. Students developed lab skills while simultaneously learning about course content. Students’ progress was evaluated through a multiple choice/essay test and their lab posters that they created on the lab experiment.

Combined Metagenomic And Phenomic Approaches Identify A Novel Salt Tolerance Gene From The Human Gut Microbiome, Eamon Culligan, Julian R. Marchesi, Colin Hill, Roy D. Sleator

Department of Biological Sciences Publications

In the current study, a number of salt-tolerant clones previously isolated from a human gut metagenomic library were screened using Phenotype MicroArray (PM) technology to assess their functional capacity. PM's can be used to study gene function, pathogenicity, metabolic capacity and identify drug targets using a series of specialized microtitre plate assays, where each well of the microtitre plate contains a different set of conditions and tests a different phenotype. Cellular respiration is monitored colorimetrically by the reduction of a tetrazolium dye. One clone, SMG 9, was found to be positive for utilization/transport of L-carnitine (a well-characterized osmoprotectant) in the …

Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler

Dartmouth Scholarship

Genome-wide interrogation of DNA methylation (DNAm) in blood-derived leukocytes has become feasible with the advent of CpG genotyping arrays. In epithelial ovarian cancer (EOC), one report found substantial DNAm differences between cases and controls; however, many of these disease-associated CpGs were attributed to differences in white blood cell type distributions. We examined blood-based DNAm in 336 EOC cases and 398 controls; we included only high-quality CpG loci that did not show evidence of association with white blood cell type distributions to evaluate association with case status and overall survival.

Genome-Wide Mycobacterium Tuberculosis Variation (Gmtv) Database: A New Tool For Integrating Sequence Variations And Epidemiology, Ekaterina N. Chernyaeva, Marina V. Shulgina, Mikhail Rotkevich, Pavel Dobrynin, Serguei Simonov, Egor A. Shitikov, Dmitry S. Ischenko, Irina Y. Karpova, Elena S. Kostryukova, Elena N. Ilina, Vadim M. Govorun, Vyacheslav Y. Zhuravlev, Olga A. Manicheva, Peter K. Yablonsky, Yulia D. Isaeva, Elena Y. Nosova, Igor V. Mokrousov, Anna A. Vyazovaya, Olga V. Narvskaya, Alla L. Lapidus, Stephen J. O'Brien

Biology Faculty Articles

Background

Tuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome.

Description

Here we describe a broadly inclusive unifying Genome-wide Mycobacterium tuberculosis Variation (GMTV) database, (http://mtb.dobzhanskycenter.org) that catalogues genome variations of M. tuberculosis strains collected across Russia. GMTV contains a broad spectrum of data derived from different sources and related to M. …

Childhood Obesity And Familial Hypercholesterolemia: Genetic Diseases That Contribute To Cardiovascular Disease, Alyssa Caudle

Senior Honors Theses

Childhood obesity occurs as the result of an imbalance between caloric intake and energy expenditure. Genetic risk factors for obesity have become an area of research due to its permanency. Mutated genes such as Fat Mass and Obesity Associated (FTO), Leptin (LEP), Leptin Receptor (LEPR), Melanocortin 4 Receptor (MC4R), Adiponectin C1Q and Collagen Domain Containing (ADIPOQ), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) all contribute to the development of childhood obesity. In the presence of high cholesterol caused by obesity, the genetic condition known as familial hypercholesterolemia is exacerbated. Familial hypercholesterolemia is caused by a …

Data From: Genotyping-By-Sequencing For Populus Population Genomics: An Assessment Of Genome Sampling Patterns And Filtering Approaches, Paul G. Wolf, Martin P. Schilling, Aaron M. Duffy, Hardeep S. Rai, Carol A. Rowe, Karen E. Mock, Bryce A. Richardson

Browse all Datasets

Continuing advances in nucleotide sequencing technology are inspiring a suite of genomic approaches in studies of natural populations. Researchers are faced with data management and analytical scales that are increasing by orders of magnitude. With such dramatic advances comes a need to understand biases and error rates, which can be propagated and magnified in large-scale data acquisition and processing. Here we assess genomic sampling biases and the effects of various population-level data filtering strategies in a genotyping-by-sequencing (GBS) protocol. We focus on data from two species of Populus, because this genus has a relatively small genome and is emerging …

Α-Latrotoxin Genes Are Highly Divergent Between Species Of Widow Spiders (Genus Latrodectus), Kacy M. Bennett

Honors College Theses

Widow spiders (genus Latrodectus) possess neurotoxic venom that varies in potency among species. α-latrotoxin is the main protein in widow venom that affects vertebrates, including humans. The European black widow, Latrodectus tredecimguttatus, is currently the only species in this genus where the gene for α-latrotoxin has been characterized. The study presented here characterizes the genetic composition of α-latrotoxin from two additional species, the brown widow (L. geometricus) and the southern black widow (L. mactans). Genetic differences among the three species were quantified for α-latrotoxin. Between species genetic divergence in α-latrotoxin was also compared to …

Androgen Receptor Ggn Microsatellite In Primates, Thushari Alahapperuma

Honors Program Theses and Research Projects

The androgen receptor (AR) gene is an important gene that functions to regulate male sexual development. The first exon of this gene encodes the N-terminal domain, which controls transcriptional activity of the receptor. Also, the first exon contains two polymorphic repeats: CAG codes for the polyglutamlne tract (polyQ) while GGN codes for the polyglycine tract (polyG). Currently, more research has been done on the CAG polymorphism, while GGN has been less thoroughly studied.

A Morphological And Genetic Analysis Of Forensically Important Blow Flies, From Georgia: The Genus Lucilia, Katie S. Googe

Honors College Theses

Identification of Blow flies (Diptera: Calliphoridae) to species is important for estimating postmortem intervals, because insect species develop at different rates. Three Blow fly species in Georgia; Lucilia coeruleiviridis, L. cuprina, and L. sericata are similar morphologically, making identification difficult. Furthermore, the status of L. cuprina is in doubt; this species may be a complex of true L. cuprina, and L. cuprina x L. sericata hybrids. The objective of this study was to survey the Georgia Blow fly community and validate the statuses of L. coeruleiviridis, L. cuprina, and L. sericata, through morphological and …

Birds In Peatswamp At Klias Forest Reserve And Environs, Sabah, Malaysian Borneo, Frederick H. Sheldon, Geoffrey Davison, Anna Wong, Robert G. Moyle

Occasional Papers of the Museum of Natural Science, Louisiana State University

Periodically from 1998-2004, we surveyed birds in the Klias Forest Reserve, which is one of the last remaining pockets of peatswamp in western Sabah. We report here on those surveys. We also review prior work on birds in peatswamp and swamp forest in the Klias-Sipitang region of Sabah as it relates to the conservation of habitat and birds specialized on peatswamp. Peatswamp forest is in jeopardy from development and fires throughout Borneo, and particularly in the Malaysian State of Sabah, which had very little to start. Peatswamp in the Klias area is of particular importance for conservation and bird watching …

Effects Of Nod2/Card15 And Atg16l1 On Crohn’S Pathogenicity, Thomas J. Tibbetts

Thinking Matters Symposium Archive

Crohn’s disease is a form of inflammatory diseases of the alimentary canal, usually most affecting the small intestine. This disease may affect over 700,000 people in the United States alone, while the cause remains somewhat of a mystery. This literature review will explore the role of two specific genes (NOD2/CARD15, ATG16l1) and how they may affect the pathogenicity of Crohn’s. Both the CARD15/NOD2 and ATG16l1 genes have specific functions in immune and inflammatory response. Studies using both empirical data and in vivo laboratory results the CARD15/NOD2 gene has been found to encode a nucleotide-binding oligomerizationdomain which identifies a specific component …

Probing The Effects Of Tbhk2 On Trypanosoma Brucei Growth, Social Growth, And Inhibitor Response, Amber Hackler, William Mcalpine, Yijian Qiu, James Morris

Graduate Research and Discovery Symposium (GRADS)

In sub-Saharan Africa the protozoan parasite, Trypanosoma brucei, continues to be of major concern for the health and economic development of the region. This parasite is known to cause human African trypanosomiasis (HAT or African sleeping sickness) and nagana in livestock such as cattle. Social behaviors, such as colonization and migration, are important in the study of T. brucei because of the way the parasite infects its mammalian host. During the fly bloodmeal, the parasite first passes into the gut but then eventually migrates to the fly salivary glands where it will continue to develop before transmission as a parasitic …

Structural And Functional Analysis Of Harv1 Lipid Binding, Jamie Francisco

Graduate School of Biomedical Sciences Theses and Dissertations

Cardiovascular disease (CVD) has the highest mortality rate worldwide and is considered epidemic in the United States. Statins as the primary and almost sole method of treatment for cholesterol-related CVD, but they have limitations. Proper sterol transport is needed to maintain normal blood lipid levels. Studies have shown that misregulation of lipid trafficking aids in the progression of CVD and in the activation of the unfolded protein response (UPR). Misregulation of lipid and sterol homeostasis also results in the loss of lipid rafts, known cellular signaling hubs and major components of ER associated membrane contact sites. Arv1 is a highly …

Limited Evidence For Adaptive Evolution And Functional Effect Of Allelic Variation At Rs702424 In The Promoter Of The Tas2r16 Bitter Taste Receptor Gene In Africa, Michael Campbell

Department of Biology Faculty Publications

Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin …

Naturalized Offspring From An 85-Year-Old Chinese Chestnut (Castanea Mollissima) Planting: Stand Dynamics And Genetic Relationships, Amy Christel Miller

Open Access Theses

Chestnuts, members of the genus Castanea , family Fagaceae, are valuable worldwide, and all species have noteworthy ecological, economic, and cultural importance in their native ranges. Historically, American chestnut (Castanea dentata (Marshall) Borkh.) was an abundant tree species in eastern North America until its decimation in the early 20 th century by chestnut blight, caused by the fungus Cryphonectria parasitica . To regain the benefits of this prized species in North America, efforts are ongoing to produce and introduce blight-resistant hybrids of C. dentata and the blight-resistant Chinese chestnut ( C. mollissima Blume). It is important that the C. …

Redox Regulation Of Protein Translation In Eukaryotes, Maxim Gerashchenko

Department of Biochemistry: Dissertations, Theses, and Student Research

Gene expression may be controlled at multiple levels, e.g., through genomic architecture, transcription and translation. In the current work, we focused on regulation of protein synthesis. Historically, the investigation of the regulation of gene expression at the level of translation lagged behind the transcriptional control because of the lack of accessible high-throughput methods. Our research has begun with the finding of the use of alternative non-AUG start codon in thioredoxin-glutathione reductase (TGR), a selenoprotein involved in redox control during male reproduction. The use of this codon, CUG, relies on the Kozak consensus sequence and ribosomal scanning mechanism. However, the CUG …

Evaluating The Impact Of Genotype Errors On Rare Variant Tests Of Association, Kaitlyn Cook, Alejandra Benitez, Casey Fu, Nathan L. Tintle

Faculty Work Comprehensive List

The new class of rare variant tests has usually been evaluated assuming perfect genotype information. In reality, rare variant genotypes may be incorrect, and so rare variant tests should be robust to imperfect data. Errors and uncertainty in SNP genotyping are already known to dramatically impact statistical power for single marker tests on common variants and, in some cases, inflate the type I error rate. Recent results show that uncertainty in genotype calls derived from sequencing reads are dependent on several factors, including read depth, calling algorithm, number of alleles present in the sample, and the frequency at which an …

Relating The Metatranscriptome And Metagenome Of The Human Gut, Eric A. Franzosa, Xochitl C. Morgan, Nicola Segata, Levi Waldron, Joshua Reyes, Ashlee M. Earl, Georgia Giannoukos, Matthew R. Boylan, Dawn Ciulla, Dirk Gevers, Jacques Izard, Wendy S. Garrett, Andrew T. Chan, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

Although the composition of the human microbiome is now well-studied, the microbiota’s > 8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. …

Stress Responses And Energy Storage In Drosophila Melanogaster Selected For Resistance To A Gram-Positive Bacillus Cereus Spores, Zhen Hu

School of Biological Sciences: Dissertations, Theses, and Student Research

A survival response study was carried out by using D. melanogaster and the opportunistic pathogen B. cereus as the agent of selection. The spores of B. cereus, a gram-positive bacteria that can cause the human pathogen disease, were applied in our artificial laboratory selection. Selected lines were treated with B. cereus spores. Wound control lines were punctured with a needle dipped into sterile H₂O. Control lines did not apply any treatment. Three different environmental treatments were used within each line type (autoclaved spores of B.cereus, sterile H₂O and no treatment). The autoclaved spores were …

An Lnvestigation Using Saccharornyces Cereylslae During Growth With Haloperidol On Different Carbon Sources, Elizabeth Garza

Honors Program Theses and Research Projects

Haloperidol is a first generation antipsychotic that is used to treat symptoms of psychosis in patients affected by schizophrenia. This class of antipsychotics is associated with neurological side effects. On the other hand, atypical antipsychotics, such as Clozapine, are associated with metabolic side effects. Ln order to better understand the metabolic basis for the different side effects, we compared the two classes of antipsychotics. Yeast was grown in the presence of Haloperidol on both fermentable and non fermentable carbon sources at concentrations of 0 uM, 1 uM, 5 uM, and 10 uM. The resultant cell viability and the reactive oxygen …

Effects Of Il8 And Immune Cells On The Regulation Of Luteal Progesterone Secretion, Heather Talbott, Abigail Delaney, Pan Zhang, Yangsheng Yu, Robert Cushman, Andrea S. Cupp, John S. Davis

Department of Animal Science: Faculty Publications

Recent studies suggest that chemokines may mediate the luteolytic action of PGF2α (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of IL8 on specific luteal cell types in vitro. Midcycle cows were injected with saline or PGF, ovaries were removed after 0.5 - 4 h and chemokine expression was analyzed by qPCR. In vitro expression of IL8 was analyzed after PGF administration and with cell signaling inhibitors to determine the mechanism of PGF-induced chemokine expression. Purified neutrophils were analyzed for migration and activation in response to IL8 and PGF. Purified …

Molblocks: Decomposing Small Molecule Sets And Uncovering Enriched Fragments, Dario Ghersi, Mona Singh

Interdisciplinary Informatics Faculty Publications

The chemical structures of biomolecules, whether naturally occurring or synthetic, are composed of functionally important building blocks. Given a set of small molecules—for example, those known to bind a particular protein—computationally decomposing them into chemically meaningful fragments can help elucidate their functional properties, and may be useful for designing novel compounds with similar properties. Here we introduce molBLOCKS, a suite of programs for breaking down sets of small molecules into fragments according to a predefined set of chemical rules, clustering the resulting fragments, and uncovering statistically enriched fragments. Among other applications, our software should be a great aid in large-scale …