Microbiology Commons^™

Development Of A Model For Adult T Cell Leukemia/Lymphoma In Htlv-1 Infected Humanized Mice, Kayleigh Ingersoll, Dr. Brad Berges

Journal of Undergraduate Research

Human T-lymphotropic virus type-1 (HTLV-1) is a virus that is linked to Adult T-cell leukemia/lymphoma (ATLL), causing cancer in T cells. There are an estimated 10-20 million people worldwide infected with HTLV-1. HTLV-1 is transmitted through contact of bodily fluid and usually occurs through breastfeeding, sexual transmission, and sharing needles. ATLL develops in only about 5% of infected persons after decades of infection. An ATLL diagnosis is grim as there is no cure, and most patients do not respond or only have a limited response to treatments. Current treatments include antiretrovirals or chemotherapy, but there has been little to no …

The Diversity Found Among Carbapenem-Resistant Bacteria, Galen Edward Card

Theses and Dissertations

This work will look at two factors that add to the diversity of carbapenem resistant bacteria. First, it focuses on the diversity of carbapenemase resistance plasmids. 446 plasmids were characterized by size, gene content and replicon groups. We identified that on average, over 30% of the encoded proteins on each plasmid have an unknown function. Plasmid sizes ranged from 1.6kb to 500kb, with an average of around 100kb and median of 80kb. Additionally, six replicon groups account for 80% of all the carbapenemase resistance plasmids. We also highlight the lack of data available for carbapenemase carrying plasmids from bacterial genera …

Bacteriophages For Treating American Foulbrood And The Neutralization Of Paenibacillus Larvae Spores, Thomas Scott Brady

Theses and Dissertations

The causative agent of the most devastating honeybee disease, American foulbrood (AFB), is the spore-forming bacterium Paenibacillus larvae. To prevent AFB outbreaks beekeepers prophylactically treat their hives with antibiotics even though it decreases the overall health of uninfected hives. A new treatment for AFB is needed due to recent legislation against using antibiotics, antibiotic resistance developing in P. larvae, and the resilience of P. larvae spores. Bacteriophages, or phages, are an attractive alternative to traditional antibiotics because of their specificity and ability to evolve alongside their target bacterium. In this study, two phage cocktails were developed for the …

The Ability Of Novel Phage To Infect Virulent Bacillus Anthracis Isolates, Hyrum Smith Shumway

Theses and Dissertations

Bacillus anthracis is a soil dwelling microbe with pronounced pathogenic potential. Historically, anthrax has infected livestock and man. In the modern-age, anthrax is a bioterrorism concern with major incidents every decade. While the threat of large scale attacks is currently viewed as unlikely, the threat is consistent and constant. Current methods to defend against such an attack focus on antibiotics and containment of public panic. Antibiotic resistance, while not currently an issue for anthrax, could easily become so with genetically engineered weaponized strains created by rogue states or independent actors. This project evolved from collaborations between the Grose lab and …

Identifying Novel Regulators Of Cellular Respiration, Sam Nicholes, Julianne Grose

Journal of Undergraduate Research

The impetus behind my project was to contribute in a small but meaningful way to the growing body of research for cures and treatments for cancer. Cancer is fundamentally unwanted cell growth and proliferation. Metabolic processes that take place on the cellular level are the key to finding solutions to the many worldwide problems of cancer. My project looked at some of these metabolic processes in order to help identify the control mechanisms that cause these processes to function normally or to behave aberrantly. The goal was to identify a cellular pathway that could be used as a potential target …

Borrelia Burgdorferi Invasion Of B Lymphocytes, Jacob Bailey, Richard Robinson

Journal of Undergraduate Research

The goal of this project was to determine if Borrelia Burgdorferi’s linear plasmid 36 is required for intracellular localization in B lymphocytes. A more complete understanding of the intracellular localization of B. burgdorferi may provide the means to effective Lyme treatment. It has been proposed that intracellular localization of Lyme spirochetes may be, at least in part, responsible for Post Treatment Lyme Disease. As the spirochetes are safe within human cells, Borrelia are able to evade host immune system responses and be protected from antibiotic treatment. A more complete understanding of the intracellular localization of B. burgdorferi may provide the …

Biomarker Analysis And Clinical Relevance Of Thymidine Kinase 1 In Solid And Hematological Malignancies, Evita Giraldez Weagel

Theses and Dissertations

Despite the global effort to discover and improve ways to detect, treat, and monitor cancer, it still remains the second leading cause of death in the United States and poses a major health and economic burden worldwide. While traditional treatments like surgery, chemotherapy, radiation therapy, and hormone therapy have been successful and have decreased cancer mortality, cancer incidence in all sites continues to rise. Consequently, there is an immediate need to find new therapeutics for the treatment of cancer. In recent years, and with the continuing push towards personalized medicine, cancer biomarkers have become crucial to detect, treat, and monitor …

Discovery Of Geographical Gene Variants In Related Pseudomonas Aeruginosa Bacteriophages, Emilee Carr, Elise Melhado, Emily Loertscher, Trever Thurgood, Ruchira Sharma, Julianne H. Grose

Library/Life Sciences Undergraduate Poster Competition 2019

Antibiotic resistant bacterial strains are a major crisis in the world due to the difficult nature of curing individuals afflicted with them. Phage therapy has been proposed as an alternate treatment for these bacterium. In Dr. Julianne Grose's lab, bacteriophages were against the bacteria, Pseudomonas aeruginosa. To isolate, environmental samples were utilized in enrichment cultures that were ultimately used in serial dilutions, plaque purification, electron microscopy, DNA isolation, sequencing, and genome annotation. The P. aeruginosa phage, TF17, infects a bacterial strain that is highly related to a strain that causes fatalities as an opportunistic infection in patients with cystic fibrosis. …

Hospital And Meat Associated Staphylococcus Aureus And Their Biofilm Characteristics, Trevor Michael Wienclaw

Theses and Dissertations

Biofilm phenotypes were studied in 32 Staphylococcus aureus strains isolated from store-bought meats and 22 from diseased patients in hospitals. Of the meat-associated strains, 21 were methicillin-resistant Staphylococcus aureus (MRSA) and 11 were methicillin-susceptible Staphylococcus aureus (MSSA). The hospital-associated strains included 15 MRSAs and 7 MSSAs. We studied the robustness and composition of the biofilms produced by these strains. We found that on average hospital-associated strains form more robust biofilms than meat associated strains. The model often used to describe S. aureus biofilm composition includes two biofilm types defined by the presence or absence of polysaccharide intercellular adhesin (PIA), PIA-dependent …

Povidone-Iodine Vapor Kills Mrsa, Benjamin Ogilvie, Jon Mitton, Jordan Tucker, Dennis L. Eggett, Richard A. Robison

Student Works

Povidone-iodine is an antiseptic that is frequently used to clean skin prior to surgery. Current FDA regulations require that hospitals dispense povidone-iodine from single-use bottles, rather than large, multi-use containers, to prevent microbial contamination. This results in hospitals generating lots of product waste. However, if povidone-iodine vapor can kill microbes, then multi-use containers may be safe to use, since any bacteria that contaminated the inside of the container would soon die. The purpose of this research was to determine whether vapor from povidone-iodine could kill methicillin-resistant Staphylococcus aureus (MRSA), a common cause of hospital-associated infections.

In summary, this experiment demonstrated …

Influence Of Epstein-Barr Virus On Systemic Lupus Erythematosus Disease Development And The Role Of Depression On Disease Progression, Caleb Cornaby

Theses and Dissertations

Systemic Lupus Erythematosus (SLE) is an autoimmune disease affecting 20 to 250 individuals per 100,000 worldwide. Symptomology includes dermatological manifestations such as discoid lesions, acute cutaneous rashes, and oral and nasal ulcers, along with musculoskeletal, pulmonary, and renal complications. Abnormal T and B lymphocyte function and apoptosis, immune complex clearance, complement function, and nucleosome processing are typical of disease pathophysiology. SLE is the result of both environmental and genetic factors, which together create the conditions leading to disease onset and progression. Of these environmental factors, Epstein-Barr virus (EBV) infection is known to cause the genesis of cross-reactive antibodies in SLE …

Acetobacter Fabarum Genes Influencing Drosophila Melanogaster Phenotypes, Kylie Makay White

Theses and Dissertations

Research in our lab has predicted hundreds of bacterial genes that influence nine different traits in the fruit fly, Drosophila melanogaster. As a practical alternative to creating site-directed mutants for each of the predicted genes, we created an arrayed transposon insertion library using a strain of Acetobacter fabarum DsW_054 isolated from fruit flies. Creation of the Acetobacter fabarum DsW_054 gene knock-out library was done through random transposon insertion, combinatorial mapping and Illumina sequencing. Successful mapping of transposon insertion was achieved for 6418 mutants with hits within 63% of annotated genes within Acetobacter fabarum DsW_054. Insertion sites were verified in …

Phosphate Signaling Through Alternate Conformations Of The Pstscab Phosphate Transporter, Ramesh Krishna Vuppada

Theses and Dissertations

Phosphate is an essential compound for life. Escherichia coli employs a signal transduction pathway that controls the expression of genes that are required for the high-affinity acquisition of phosphate and the utilization of alternate sources of phosphorous. These genes are only expressed when environmental phosphate is limiting. The seven genes for this signaling pathway encode the two-component regulatory proteins PhoB and PhoR, as well as the high-affinity phosphate transporter PstSCAB and an auxiliary protein called PhoU. As the sensor kinase PhoR has no periplasmic sensory domain, the mechanism by which these cells sense environmental phosphate is not known. This paper …

Final Report For The 2015 Meg Entitled: Development Of Real-Time Polymerase Chain Reaction (Q-Pcr) Assays For The Detection And Identification Of Human Tick-Borne Pathogens, Richard Robison

Journal of Undergraduate Research

1. Develop singleplex q-PCR assays to identify the tick-borne pathogens Borrelia burgdorferi, Borrelia hermsii, Bartonella henselae, and Babesia microti. Primer generation software will be used to design primer and probe sequences that will theoretically perform optimally in PCR reactions. All sequences will be subjected to BLAST searches to confirm their specificity for a particular organism. Once primer sequences have been obtained, they will be synthesized by Integrated DNA Technologies, Inc. (IDT). These primers will be evaluated in q-PCR reactions using target DNA from multiple isolates and SyberGreen to detect nucleic acid amplification. Parameters for each reaction will be optimized using these …

Autoimmunity-Promoting B Cell Effects Of The Risk Factor Irf5, Brian Poole

Journal of Undergraduate Research

The academic objectives of this proposal were met. Using the funding provided by the MEG, we generated data that were used to publish two peer-reviewed journal articles:

The Chemotherapeutic Potential Of Resveratrol-Based Treatments, Connor Peck, Kim O'Neill

Journal of Undergraduate Research

Cancer is one of the most prevalent and deadly diseases in the world. In 2012 alone, there were approximately 14 million new cases of cancer and over 8 million cancer-related deaths worldwide. Despite extensive research in past decades, the burden of cancer continues to increase.

One of the most common treatments for cancer is chemotherapy, the use of various chemical substances that exhibit anti-cancer activity. Unfortunately, chemotherapy can be quite toxic and often produces inadequate results. There remains a great need for improved chemotherapeutic treatment strategies in order to improve outcomes for cancer patients.

The purpose of my project was …

Effect Of High Expression Of Irf5 On B Cell Activation After Antigen Stimulation, Kalarelyn Eberting, Brian Poole

Journal of Undergraduate Research

While autoimmune diseases are very prevalent in the United States, little is understood about the cause of autoimmunity, making it difficult to take preventative measures and develop treatments. Previous studies have determined that a common genetic risk factor across many autoimmune diseases leads to B cell overexpression of the transcription factor IRF5 (1,2,4). Researchers have also discovered that high IRF5 levels are strongly associated with autoantibody production, suggesting that IRF5 may play a role in actually causing autoimmunity. At this point, however, it is unclear how IRF5 promotes the production of autoantibodies.

Cellular Mechanism Of Thymidine Kinase 1 Secretion, Wei Meng, Kim O'Neill

Journal of Undergraduate Research

Cancer remains the second most common cause of death in the US, accounting for nearly 1 of every 4 deaths. Studies have shown that the early detection of cancer leads to better patient prognosis and a greater five-year survival rate. [1] Diagnostic and prognostic markers play a key role in classifying tumors and determining the best treatment plan for a patient. Among these biomarkers, Thymidine kinase 1 (TK1) has been studied extensively, primarily as a diagnostic biomarker for a variety of cancer types. TK1 plays a role in regulating the intracellular thymidine pools throughout the cell cycle, and thus regulates …

Phenome-Wide Association Study Of Y Chromosome Genetic Markers, Matthew Durrant, Mary Davis

Journal of Undergraduate Research

The purpose of this project was to analyze genetic variants on the Y chromosome for significant association with various diseases. In Dr. Mary Davis’ lab we gained access to a unique data set that allows us to analyze many single-nucleotide polymorphisms (SNPs) on the Y chromosome. This was a hypothesis-generating study that has the potential to revolutionize the currently accepted hypothesis that genetic variants on the Y chromosome do not play a significant role in common disease.

Expression Changes Of Dopamine Type 2 Receptor On The Surface Of Human Monocytes And Lymphocytes After Exposure To Dopamine In Vitro., Brandon Thomas Garcia, Sandra Hope, Scott Steffensen

Journal of Undergraduate Research

Dopamine (DA) is a neurotransmitter in the brain that plays a role in several functions such as reward, motivation, and dependence. The imbalance of DA in the central nervous system (CNS) can lead to several debilitating diseases like Parkinson’s Disease, Alzheimer’s, and Schizophrenia as well as drug dependence. Levels of DA in the brain are often determined by measuring the expression of Dopamine type 2 (D2) receptors by positron emission topography (PET) scans in the Nucleus Accumbens (NAc). This test which is often expensive and unavailable to many people without access to hospitals or regular healthcare.

Development Of Chimeric Antigen Receptor T Cells To Target Cancer, Justin Crandall, Dr. Scott Weber

Journal of Undergraduate Research

Cancer negatively affects the lives of millions of individuals, and remains a difficult ailment to treat. In 2014, approximately 585,720 deaths and 1,665,540 new cases of cancer were reported in the USA alone.1 Treatment of cancer is challenging due to cancer mutating to combat the body’s immune system. An example is shown in major histocompatibility complexes (MHCs) located on the surface of nearly every cell. These are patrolled by T cells to ensure that cells are properly functioning and healthy. With cancer however, these become downregulated allowing the cancer to grow and proliferate since T cells are unable to detect …

Development Of A Model For Adult T Cell Leukemia In Htlv-1 Infected Humanized Mice, Matthew Smith, Dr. Brad Berges

Journal of Undergraduate Research

Millions of people in the world are infected with human T-lymphotropic virus type-1 (HTLV-1). As the name states, this virus attacks the T cells of the infected organism. Though many of these individuals will remain asymptomatic throughout life, a small percentage will develop adult T cell leukemia/lymphoma (ATLL), a rare and understudied form of cancer. The latency period, or amount of time between infection and detection of cancer, is generally 20-40 years before infected patients begin developing cancer.

Creation Of Twelve Member Plasmid Library For Promoter Swapping To Control Chromosomal Gene Expression In E. Coli, Chris Nielson, William R. Mccleary

Journal of Undergraduate Research

Metabolic engineering is becoming a very important area of research, allowing researchers to harness metabolic pathways to either eliminate or synthesize desired compounds. Understanding metabolic pathways by altering expression of proteins involved in the pathway helps to uncover thermodynamic bottlenecks which render certain pathways inefficient or infeasible. Altering expression of genes through the use of promoter swapping is a useful research technique used to understand important metabolic and physiologic pathways. Engineered promoters contained in plasmids can be inserted into chromosomal DNA through the utilization of promoter swapping to alter the expression of a given gene in order to better understand …

Thymidine Kinase 1: The Key To Predicting Cancer Recurrence, Rachel Brog, Dr. Kim L. O'Neill

Journal of Undergraduate Research

Currently it is estimated that over 230,000 women will be diagnosed with breast cancer this year in the United States alone. Although treatments are improving, an alarming number of these cases will show cancer recurrence after treatment. A method to consistently predict cancer recurrence is crucial to better treat cancer and improve patient care. Thymidine Kinase 1 (TK1) has been found in abnormally high levels in serum and tissue of cancer patients compared to healthy patients. There is question to why TK1 is present in such high quantities when normally it aids in the DNA salvage pathway during S phase …

The Effects Of Nucleosome Positioning And Chromatin Architecture On Transgene Expression, Colton E. Kempton

Theses and Dissertations

Eukaryotes use proteins to carefully package and compact their genomes to fit into the nuclei of their individual cells. Nucleosomes are the primary level of compaction. Nucleosomes are formed when DNA wraps around an octamer of histone proteins and a nucleosome's position can limit access to genetic regulatory elements. Therefore, nucleosomes represent a basic level of gene regulation. DNA and its associated proteins, called chromatin, is usually classified as euchromatin or heterochromatin. Euchromatin is transcriptionally active with loosely packed nucleosomes while heterochromatin is condensed with tightly packed nucleosomes and is transcriptionally silent. In order to become active, heterochromatin must first …

Comparison Of Cytokine Expression And Bacterial Growth During Periparturient And Mid Lactation Mastitis In A Mouse Model, Rhonda Nicole Chronis

Theses and Dissertations

Clinical cases of bovine mastitis are most severe in the early stages of lactation. The causes of this increased propensity for severe mastitis during early lactation, compared to mid and late lactation are unclear. In order to better understand the early lactation immune response to mastitis, a murine model of mastitis was employed. Intramammary inoculation of a mastitis causing Escherichia coli strain was performed in lactating mice at various stages of lactation to model the immune response seen in cows during lactation. In our experiments, mice in the early stages of lactation exhibited altered mRNA expression of cytokines IL-1β, IL-6, …

Characterization Of Neuronal Nicotinic Acetylcholine Receptors And Their Positive Allosteric Modulators, Doris Clark Jackson

Theses and Dissertations

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are necessary in memory and cognition. They are pentameric and consist of α and β subunits. They are most commonly heteromeric but, can sometimes be homomeric. nAChRs are activated by many ligands including nicotine (exogenous) and acetylcholine (endogenous).nAChRs are located on hippocampal interneurons. The interneurons, although sparse, control the synchronous firing of the pyramidal cells. However, the hippocampal interneuron structure and function is quite diverse and not fully characterized. Therefore, we sought to quantify nAChR subunit mRNA levels using real-time PCR of CA1 hippocampal interneurons.Surprisingly we found that the α3 …

The Role Of Pas Kinase And Cbf1 In Cellular Metabolism, Jenny Adele Pattison, Julianne H. Grose

Journal of Undergraduate Research

The most recent National Institute of Health report concludes that 68.8% of American adults are considered to be overweight or obese1. With this trend in obesity, metabolic diseases such as heart disease, stroke, cancer, and diabetes are on the rise. The critical yet basic function of cellular homeostasis is a central component in controlling these diseases. Sensory protein kinases are essential in the phosphorylation of many protein substrates, allowing them to control several metabolic functions and appropriately allocate glucose, maintaining homeostasis in cells. PAS kinase is a sensory protein kinase that is highly conserved and plays a crucial role in …

Bacteriophages As A Biocontrol Agent Of Soft Rot In Potatoes, Trevor Hodson, Don Breakwell

Journal of Undergraduate Research

Pectobacterium carotovorum (Pcc) is a principle causative agent of soft rot in potatoes. It causes losses of up to 60% in potato yields in the USA (Mantsebo et. Al, 2014) and approximately $50-$100 million dollars’ worth of losses yearly in multiple types of crops. Because potatoes grow beneath the soil surface, there is no way of treating the potatoes until they are harvested. Even then, no postharvest methods of controlling this pathogen exist (Wood et. Al, 2013). A spray-able bacteriophage cocktail specific to Pcc could save millions of dollars-worth of crops each year by minimizing soft rot.

A Phenome Wide Association Study Of Multiple Sclerosis And Comorbidities, Scott Frodsham, Mary Davis

Journal of Undergraduate Research

Genome wide association studies (GWAS) have identified relationships between many different genes and diseases. GWAS studies scan whole genomes of many individuals and then associate genetic variants with diseases that the individuals have. In contrast, a phenome wide association study (PheWAS), looks at the phenotypes of many individuals and associates those phenotypes with one or more genetic variants. Electronic medical records (EMRs) linked to DNA biobanks provide both clinical and genetic data of patients. This study utilizes one such EMRlinked DNA biobank called BioVU from Vanderbilt University.