Life Sciences Commons^™

Metabolic Heterogeneity And The Roles Of Cody And Ccpa In Central Metabolism And S. Aureus Biofilm Formation., Logan L. Bulock

Theses & Dissertations

Staphylococcus aureus is a metabolically versatile human pathogen, causing disease in many areas of the body. Its versatility can be attributed to the fact that it utilizes a variety of tools to adapt to many different environments, including toxins to scavenge from the host and multiple transporters to compete for its preferred carbon sources. S. aureus can also survive in harsh conditions through biofilm development, which are notoriously recalcitrant to antibiotics and immune defenses. Biofilms exhibit marked heterogeneity, with division of labor for production of matrix components and differential gene expression among various niches within the biofilm.

In this study, …

Metabolic Regulation During Extraembryonic Endoderm Differentiation, Mohamed Gatie

Electronic Thesis and Dissertation Repository

The inner cell mass undergoes orchestrated cellular divisions resulting in the formation of the epiblast (EPI) and primitive endoderm (PrE). Understanding the process of cell fate specification is crucial to appreciate the intricacies of proper embryonic development. While the mouse embryo is an excellent model, limitations do exist with number, technical challenges, and accessibility, therefore, in my thesis I employed two cell-based models to recapitulate the EPI-PrE fate in vitro. Many signaling pathways have been implicated in this lineage decision, metabolism and its downstream products have been recently regarded as a driver of lineage commitment. Using various biochemical, molecular, …

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse

Arts & Sciences Electronic Theses and Dissertations

Malaria is an enormous financial and public health burden for much of the world, infecting over 200 million and killing over 400,000 people every year. While much progress has been made combating malaria in the past few decades, those advances have slowed in recent years, partially due to the emergence of resistance to all known antimalarials used to date. To achieve the goal of eliminating malaria as a major global health problem, new therapeutics need to be developed, targeting novel categories of parasite biology. One poorly understood area of parasite biology is the regulation of various metabolic pathways. We have …

Link Between Muscle And Whole-Body Energetic Responses To Exercise, Christopher M.T. Hayden

Masters Theses

Substantial evidence exists regarding how skeletal muscles use energy and how this affects muscular performance. What remains unclear is how characteristics of muscle energetics affect whole-body energetics during daily living, and what effects this may have on mobility. The goal of this study was to determine the associations between muscle and whole-body energetics including the relationships between: 1) muscle PCr depletion (∆PCr) in response to light intensity isotonic contractions and the oxygen deficit at the onset of a 30-min treadmill walk (30MTW), and, 2) muscle oxidative capacity and excess post-exercise oxygen consumption (EPOC; 30MTW), respiratory exchange ratio (RER; 30MTW), and …

Characterization And Modulatory Influence Of Pyruvate Kinase Muscle Isoforms 1 And 2 Within The Murine Pluripotent Continuum, Joshua G. Dierolf

Electronic Thesis and Dissertation Repository

Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) represent opposite ends of a pluripotency continuum, respectively referred to as naïve and primed pluripotent states. A third, recently discovered intermediate state has been described as the ‘formative state’. Metabolism has been traditionally regarded as a by-product of cell fate; however, recent evidence now supports metabolism as promoting stem cell fate. Pyruvate kinase muscle isoforms 1 and 2 (PKM1 and PKM2) catalyze the final, rate limiting step of glycolysis generating adenosine triphosphate (ATP) and pyruvate; however, the precise role(s) of these isozymes in naïve, formative, and primed pluripotency is …

Decreased Activity Of Phosphofructokinase-1 In Flight Muscle Cells Of Hawk Moth Manduca Sexta With Age, Owen G. Alvine

Honors Thesis

The phosphofructokinase-1 (PFK-1) enzyme is important for the catalyzation and regulation of glycolysis, especially in muscle. Investigating age-related changes in PFK-1 activity will provide insights into the metabolism shifts in muscle cells of our muscle aging model. The hawk moth, Manduca sexta, was chosen as the model organism because of its unique endothermic, synchronous flight muscles that are more analogous to vertebrates than invertebrate species. We hypothesized that PFK-1 activity will increase in muscle cells of aged moths due to dysregulation of the mitochondria. This was predicted to change the method of energy production, by hindering oxidative phosphorylation, making glycolysis …

Catabolism Of Bcaas And Application, Skylar Arellano-Myers

Honors Thesis

Over the past 150 years, amino acids have been found and researched in the nutrition biochemistry field. Over these years, three have been identified; leucine, valine and isoleucine; to make up the branch chain amino acids (BCAAs) that play a crucial role on the anaerobic and aerobic energy systems. The metabolism of BCAAs is a highly complicated process that is regulated by the activation of the alpha-keto acids dehydrogenase complex (BCKDH complex) to complete the catabolic reaction. With exercise, it has been found to increase the metabolism of BCAAs by increasing the BCKDH complex, which will decrease the fatigue and …

Differential Gene Expression In Starvation Selected Drosophila Melanogaster, Katherine Schultz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Fruit flies that have been selected for starvation resistance can be used in experimental studies to study physiological processes. Both their genomes and their phenotypes, especially metabolism, change significantly as a result of artificial selection. Starvation selected flies develop slower and are larger due to higher lipid content as adults. We used RNAseq to study gene expression in third instar larval fat body tissue from selected and control lines at the same chronological time point, when the fed control (“FC”) lines were wandering, and the starvation selected (“SS”) lines were in the third larval instar but not yet wandering due …

Construction And Analysis Of Three Multi-Partite Synthetic Microbial Communities, Alexander J. Lazzara, Jacob K. Fanning

Honors Theses

Microbial Communities are of interest to molecular biologists hoping to understand the nature of metabolic interactions between co-existing, or possibly mutualistic, organisms. These interactions are ubiquitous in nature, but understanding the molecular mechanisms involved remains challenging and not well understood. Here, we design three tri-partite microbial circuits based on possible interactions among involved microbes, which are discussed and may suggest mutualistic interactions. Carbon and nitrogen molecular pathways and the intracellular metabolism of each microbe is discussed. We present minimal growth media that will ensure that organisms utilize available resources, which may originate from metabolic processes in neighboring microbes, simulating a …

How Acetylation Regulates Metabolic Enzyme Function During Environmental Shifts, Jared Canonigo

Biological Sciences Undergraduate Honors Theses

Organisms such as Saccharomyces cerevisiae can regulate the mechanisms of proteins through post-translational modification. These modifications play a vital role in functional proteomic activity because they can regulate protein activity, localization, and interaction with other cellular molecules. Such modifications include phosphorylation, methylation, and acetylation. The metabolic mechanisms of yeast became of keen interest to our lab because our lab noticed many stress defense proteins were being acetylated during stress heat shock. Notably, Adh1p and Adh2p showed both an increase and a decrease in acetylation at two lysine residues (K315 and K314) overtime during heat shock respectively, though the exact function …

Investigating A Novel Function For Phosphoserine Aminotransferase 1 (Psat1) In Epidermal Growth Factor Receptor (Egfr)-Mediated Lung Tumorigenesis., Rumeysa Biyik-Sit

Electronic Theses and Dissertations

Phosphoserine aminotransferase 1 (PSAT1) catalyzes the second enzymatic step within the serine synthetic pathway (SSP) and its expression is elevated in numerous human cancers, including non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutant NSCLC is characterized by activating mutations within its tyrosine kinase domain and accounts for 17% of lung adenocarcinomas. Although elevated SSP activity has been observed in EGFR-mutant lung cancer cells, the involvement of PSAT1 in EGFR-mediated oncogenesis is still unclear. Here, we explore a putative non-canonical function for PSAT1 using biochemical approaches to elucidate unknown interacting proteins and genomic RNA-seq profiling to identify cellular …

Interregulation Between Msaabcr Operon And Ccpe To Determine Staphylococcal Metabolism And Virulence, Erin R. Cox

Honors Theses

Staphylococcus aureus is a complex human pathogen that causes problems in both healthcare and community settings. Staphylococcus aureus is a gram-positive, sphere shaped bacterium that usually colonizes in the nasal cavity of healthy individuals. Staphylococcus aureus infections are a growing health concern due to its ability to produce virulence factors, such as pigmentation, protease production, and capsule formation. Two regulators in S. aureus virulence factors are msaABCR, which is a newly characterized operon, and ccpE. In order to determine the interaction between these two regulators in regulating virulence and metabolism in S. aureus, ccpE and ccpE/ …

Study Of The Role Of The Msaabcr Operon In Tricarboxylic Acid Cycle Activity And Persister Cell Formation In Staphylococcus Aureus, Karsen Motter

Honors Theses

Staphylococcus aureus is an important human pathogen that causes wide arrays of infections ranging from minor skin infections to lethal systemic conditions such as infective endocarditis, osteomyelitis, sepsis and pneumonia. These systemic diseases are often difficult to treat due to the presence of persister cells. Persister cells are a phenotypic variant of the bacterial population that exhibit extreme and transient antibiotic tolerance accompanied by a transient halt in growth. Upon cessation of antibiotic treatment, however, persisters resume growth which results in recurrence of infections. This characteristic of persister cells therefore displays high clinical significance. In this study, we show the …

Evolution And Selection: From Suppression Of Metabolic Deficiencies To Bacteriophage Host Range And Resistance, Daniel Kurt Arens

Theses and Dissertations

The evolution and adaptation of microorganisms is so rapid it can be seen in the time frame of days. The root cause for their evolution comes from selective environmental pressures that see organisms with beneficial mutations survive otherwise deadly encounters or outperform members of its population who fail to adapt. This does not always result in strict improvement of the individual as in the case of antibiotic resistant bacteria who often display fitness tradeoffs to avoid death (see Reviews [1-3]). For example, when an ampicillin resistance gene (ampC) containing plasmid that is occasionally found in the wild was transformed into …

Metabolic Reprogramming By Dna Tumour Viruses, Martin Prusinkiewicz

Electronic Thesis and Dissertation Repository

Viruses are the etiological agents of approximately 12% of human cancers. However, only a subset of viral infections eventually progress to cancer. As obligate intracellular parasites, viruses create a host-cell environment that is amenable to virus replication. These changes to host-cell processes during infection are enacted by virally-encoded proteins that act as molecular hubs. When these processes intersect with pathways that encourage the development of cancer, such as the p53 tumour suppressor pathway, these virally-encoded molecular hub proteins function as viral oncoproteins. One major requirement of both virus infected cells and rapidly growing cancer cells is an altered metabolism that …

Caffeine Modulation Of Attention And Focus In Task Performance, Claudia R. Berger

Dissertations, Theses, and Capstone Projects

Caffeine has been a heavily researched drug for decades given its prevalence in global consumption, as well as its large impacts on metabolic and executive function research alike. The present study aims to combine a behavioral study (Experiment 1) with a feasibility study (Experiment 2) to test the impacts of variable caffeine consumption on task performance. For both studies, participants filled out a questionnaire regarding caffeine use. Experiment 1 examined whether caffeine modulated attention in an online behavioral task in which participants were asked to identify a target (e.g., female “ahpa”). Participants were tested twice once after consuming 12 ounces …

The Effects Of Temperature And Body Size On The Metabolism And Hypoxia Tolerance Of White Abalone (Haliotis Sorenseni) And Red Abalone (H. Rufescens), Stephanie Fan

Theses

In 2001, white abalone, Haliotis sorenseni, became the first marine invertebrate to be listed under the U.S. Endangered Species Act. Allee effects due primarily to overharvesting and disease resulted in individuals being too far apart for successful fertilization. Despite the fishery closure in 1996, H. sorenseni still shows no signs of recovery. Today, the White Abalone Recovery Consortium (WARC), a group that includes federal and state agencies, aquaculture organizations, academic institutions, and public aquaria, is working to recover this endangered species back from the brink of extinction.

In order to better understand the metabolic demands and hypoxia tolerance of the …

Homeostatic T Cell Receptor Interactions With Self-Peptide Tune Cd4+ T Cell Function, Juliet Marie Bartleson

Arts & Sciences Electronic Theses and Dissertations

Homeostatic T Cell Receptor Interactions with Self-Peptide Tune CD4+ T Cell Function

by

Juliet Marie Bartleson

Doctor of Philosophy in Biology and Biomedical Sciences

Immunology

Washington University in St. Louis, 2021

Professor Paul M. Allen, Chair

Mature CD4+ T cells circulate throughout peripheral secondary lymphoid organs using their T cell receptor (TCR) to surveil peptide presented on major histocompatibility complex class II molecules (pMHC) in search of cognate, antigenic peptide. In the absence of an immune challenge, however, the TCR is continuously interacting with self-pMHC, which induces a relatively weak TCR signal known as tonic signaling. These homeostatic TCR:self-pMHC interactions …

Cold-Induced Metabolic Changes In Lean, Nag-1 Transgenic Mice, Rachel J. Davey

All Master's Theses

Obesity is a multifaceted metabolic disorder with severe worldwide public health consequences. While obesity can often be treated using diet and exercise, there are complex genetic interactions driving obesity that don’t always respond to such changes. One important research focus for addressing genetic factors is activating brown adipose tissue which increases thermogenesis, the process of burning stored fats to generate heat. Cold exposure is a known way to activate brown adipose tissue through b3-adrenergic signaling. This signaling pathway causes an upregulation of thermogenesis in brown adipocytes and beige adipocytes, which is white adipose tissue that “browns” and becomes metabolically active. …

Delineating The Role Of Fatty Acid Metabolism To Improve Therapeutic Strategies For Colorectal Cancer, James Drury

Theses and Dissertations--Toxicology and Cancer Biology

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the world, comprising over 1 million new cases each year and over 500,000 deaths. CRC, when detected at an early stage of disease development, can be effectively treated, with a 5-year survival rate of over 90%. Such standard treatments include surgical resection of the primary tumor in combination with adjuvant chemotherapy. However, even with advancements in surgical procedures and chemotherapeutic targets, when CRC progresses to a more advance stage, the 5-year survival rate decreases significantly to just under 14%. This stark decrease in patient survival rate can be directly …

Mechanisms And Therapeutic Interventions For Breast Cancer-Induced Fatigue And Mitochondrial Dysfunction, David Andrew Stanton

Graduate Theses, Dissertations, and Problem Reports

According to the latest statistics from the National Cancer Institute (NCI), about 1 in 8 U.S. women (~13%) will develop invasive breast cancer over the course of their lifetime. This translates to an estimated 268,600 new cases of breast cancer for the year 2019, and these diagnoses will collectively make up 15% of all new cancer cases across all cancer types. The majority of these women will experience the often-debilitating symptom of breast cancer-induced fatigue. these patients often have difficulty performing normal activities of daily living, have decreased tolerance to traditional tumor-directed therapies, and have higher rates of cancer recurrence. …