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Articles 481 - 510 of 1126
Full-Text Articles in Biology
Regulation Of Gut Commensal-Specific T Cell Differentiation By Dendritic Cell Subsets, Emilie Russler-Germain
Regulation Of Gut Commensal-Specific T Cell Differentiation By Dendritic Cell Subsets, Emilie Russler-Germain
Arts & Sciences Graduate Student Theses and Dissertations
The mammalian gastrointestinal tract can harbor both beneficial commensal organisms important for host health, but also pathogenic organisms capable of intestinal damage. It is therefore important that the host immune system mounts appropriate responses to different intestinal organisms – promoting tolerance to some, controlling the colonization of others, and inducing sterilizing immunity in cases of noxious pathogens. Failure to induce tolerance to commensal organisms may underlie immune-mediated diseases such as human inflammatory bowel disease, while inappropriate tolerance to more harmful organisms has the potential to result in infection, inflammation, or even malabsorption. Adaptive immune responses to intestinal commensal organisms are …
Comprehensive Characterization Of The Genetic And Neoantigen Landscapes Of Follicular Lymphoma Patients Supports The Feasibility Of Personalized Cancer Vaccine Treatments, Cody Alexander Ramirez
Comprehensive Characterization Of The Genetic And Neoantigen Landscapes Of Follicular Lymphoma Patients Supports The Feasibility Of Personalized Cancer Vaccine Treatments, Cody Alexander Ramirez
Arts & Sciences Graduate Student Theses and Dissertations
Follicular lymphoma (FL) is the most common indolent non-Hodgkin’s lymphoma; however, it remains incurable with conventional therapies and is poorly responsive to checkpoint blockade. FL arises from B-lymphocytes and develops slowly (and often asymptomatically). A major research focus has been on how to avoid chemotherapy treatments, to limit the potential development of treatment-related side effects, and the risk of therapy-related second cancers. FL also carries an approximately 30% lifetime risk of transforming from an iNHL to more destructive lymphomas, which are associated with poorer prognosis. The most common transformation results in diffuse large B-cell lymphoma (DLBCL). However, many patients may …
Genetic Variations In The Regulation And Biosynthesis Of Polycyclic Tetramate Macrolactams, Yunci Qi
Genetic Variations In The Regulation And Biosynthesis Of Polycyclic Tetramate Macrolactams, Yunci Qi
Arts & Sciences Graduate Student Theses and Dissertations
Streptomyces are Gram-positive and filamentous bacteria with high-G+C genomes, which have yielded over half of all clinically used antibiotics plus many other useful compounds. Genome analyses indicate that these bacteria possess biosynthetic gene clusters (BGCs) encoding for many more antibiotic-like compounds than they are known to produce. The apparent silence of many BGCs poses a significant roadblock to genome-mining efforts for novel drugs. To understand BGC silence, I compared several Streptomyces that harbor the widespread BGC for polycyclic tetramate macrolactam (PTM) antibiotics to explore the genetic variations that differentiate robustly expressed BGCs from silent BGCs. To test the prevalent hypothesis …
The Role Of Enampt-Mediated Systemic Nad+ Biosynthesis In Aging And Lifespan, Mitsukuni Yoshida
The Role Of Enampt-Mediated Systemic Nad+ Biosynthesis In Aging And Lifespan, Mitsukuni Yoshida
Arts & Sciences Graduate Student Theses and Dissertations
Aging is a systemic decline in tissue functions that occurs during the course of our life leading to the development of age-associated health deteriorations and ultimately to the expiration of life. Over the past few decades, population aging has become increasingly evident in many parts of the world, leading to increased prevalence of age-related disabilities and diseases. Because age is a major risk factor for many chronic diseases, extensive research effort has been spent to identify common age-associated molecular changes contributing to the pathogenesis and progression of these health issues. One such molecule identified to play a central role in …
Apolipoprotein E Immunotherapy For The Preclinical Treatment Of Alzheimer Disease And Cerebral Amyloid Angiopathy, Monica Xiong
Apolipoprotein E Immunotherapy For The Preclinical Treatment Of Alzheimer Disease And Cerebral Amyloid Angiopathy, Monica Xiong
Arts & Sciences Graduate Student Theses and Dissertations
The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease (AD), a neurodegenerative disorder that leads to cognitive dysfunction and dementia. One copy of APOE ε4 increases AD risk by 3.7-fold and two copies by 12-fold, whereas APOE ε2 is protective relative to the more prevalent ε3 allele. APOE4 accelerates the progression of AD by markedly impairing amyloid-β (Aβ) clearance and promoting excess Aβ aggregation, ultimately resulting in downstream neuroinflammation, tau pathology, and neurodegeneration. Aggregated Aβ can co-deposit with the APOE protein in the brain parenchyma as neuritic plaques and in …
Role Of Secretory Leukocyte Protease Inhibitor In Urinary Tract Infection, Anne Rosen
Role Of Secretory Leukocyte Protease Inhibitor In Urinary Tract Infection, Anne Rosen
Arts & Sciences Graduate Student Theses and Dissertations
Urinary tract infections (UTIs) affect 150 million people per year worldwide and can be difficult to diagnose and treat leaving room for other biomarkers to be used to define an infection. Secretory leukocyte protease inhibitor (SLPI), an antimicrobial protein also with antiprotease and anti-inflammatory properties, may be involved in host response to UTI. Here we use an established UPEC-UTI model to infect female Slpi knockout and wild type mice to show SLPI plays a role in microbial ecology of the bladder. Bacterial abundance is altered in urinary tracts and is positively correlated with SLPI in urine of wild type mice. …
Modularity Of Feedback For State-Dependent Guidance Of Navigation In Mouse Visual Cortex, Andrew M. Meier
Modularity Of Feedback For State-Dependent Guidance Of Navigation In Mouse Visual Cortex, Andrew M. Meier
Arts & Sciences Graduate Student Theses and Dissertations
Navigating through unpredictable environments requires an efficiently organized sensory system capable of adapting to behavioral demands. In the mammalian visual system, two adaptations which have arisen to meet these demands are parallel processing and top-down feedback of internally generated expectations and contextual information for adjusting responses to match the needs of the current behavioral task. Mouse visual cortex exhibits the latter of these organizing principles, like other mammals, in the form of a molecular layer (Layer 1) which receives feedback to contextually adapt sensory responses from the outside world. The first of these organizing principles, parallel processing streams, generally takes …
Examining Early Interactions Between Innate Airway Resident Immune Cells And Mtb-Specific Factors During Pulmonary Infection With Mycobacterium Tuberculosis, Micah D. Dunlap
Arts & Sciences Graduate Student Theses and Dissertations
Mycobacterium tuberculosis (Mtb) is the leading cause of death by an infectious agent in the world today, infecting roughly one quarter of humans. Despite this, the mechanisms of early pathogenesis and host protective innate immune responses remain poorly understood and uncharacterized.Lung resident Alveolar Macrophages (AMs) are the first host contact with Mtb bacilli after inhalation and are thus key mediators of the early pulmonary immune response. AMs are generally believed to reside entirely in the airway, but it was recently demonstrated that they have the capacity to egress and enter into granulomas during pulmonary infection with hypervirulent Mtb. Furthermore, we …
Understanding And Exploiting Protein Allostery And Dynamics Using Molecular Simulations, Sukrit Singh
Understanding And Exploiting Protein Allostery And Dynamics Using Molecular Simulations, Sukrit Singh
Arts & Sciences Graduate Student Theses and Dissertations
Protein conformational landscapes contain much of the functionally relevant information that is useful for understanding biological processes at the chemical scale. Understanding and mapping out these conformational landscapescan provide valuable insight into protein behaviors and biological phenomena, and has relevance to the process of therapeutic design.While structural biology methods have been transformative in studying protein dynamics, they are limited by technicallimitations and have inherent resolution limits. Molecular dynamics (MD) simulations are a powerful tool for exploring conformational landscapes, and provide atomic-scale information that is useful in understanding protein behaviors. With recent advances in generating datasets of large timescale simulations (using …
Measuring And Manipulating Tension-Dependent Behavior Of Mechanosensitive Ion Channels, Angela M. Schlegel
Measuring And Manipulating Tension-Dependent Behavior Of Mechanosensitive Ion Channels, Angela M. Schlegel
Arts & Sciences Graduate Student Theses and Dissertations
Mechanical forces play critical roles throughout the lives of all organisms and, as such, diverse arrays of mechanotransduction systems have evolved to detect and initiate responses to force. Many mechanotransduction systems consist of mechanosensitive (MS) ion channels, membrane pores that open in response to sufficient mechanical force. My dissertation focuses on both the study and application of force-dependent conformational changes of MS channels. I tested whether charged pore-lining residues R326 and D327 of the Arabidopsis thaliana mitochondrial MS channel MSL1 function in inward rectification or gating kinetics. Mutating these residues showed no effect on MSL1 rectification; however, these residues are …
Understanding The Roles Of Dna Methylation And Mecp2 In Neuronal Enhancer Control, Adam Clemens
Understanding The Roles Of Dna Methylation And Mecp2 In Neuronal Enhancer Control, Adam Clemens
Arts & Sciences Graduate Student Theses and Dissertations
The development of organisms relies on complex spatial and temporal patterning of gene expression to define cell types and facilitate their functions. Cis-regulatory elements in our genome are responsible for the control of gene expression across tissues and cell types. Regulation of these elements themselves depends on a balance of activation and repression through epigenetic modifications and molecular regulatory components. Disruption of cis-regulatory element control is emerging as a cause of neurodevelopmental disease. An important contributor to gene regulation in development is methylation of cytosine in DNA, disruption of which has been associated with disease. Notably, while all cell types …
Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division, Megan Cohan
McKelvey School of Engineering Graduate Student Theses & Dissertations
Across all domains of life, a defining hallmark of the onset of cell division is the formation of a cytokinetic ring at the center of the cell. Cell division is a tightly controlled process that involves various regulatory factors that modulate the assembly of the cytokinetic ring. In rod-shaped bacteria, the ring is termed the Z-ring after the protein FtsZ, which is foundational to ring formation and is the bacterial homolog of tubulin. Like tubulin, FtsZ is an assembling GTPase, where GTP binding promotes the cooperative assembly into FtsZ polymers that laterally associate to form bundles. While the GTPase domain …
Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke
Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke
McKelvey School of Engineering Graduate Student Theses & Dissertations
Post-traumatic osteoarthritis (PTOA) is a painful and debilitating disease of the synovial joint, characterized by degenerative changes to various joint tissues following traumatic joint injury. While several risk factors have been identified in the symptomatic progression of PTOA following injury, inflammation and NF-κB mediated changes are believed to significantly contribute to symptomatic joint dysfunction and pain. However, the temporal presentation of these pro-inflammatory signals following clinically relevant injury and their relationship to the development of symptomatic disease have not been thoroughly investigated. Therefore, there exists a critical need to better understand how these early inflammatory events following injury may contribute …
Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell
Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell
McKelvey School of Engineering Graduate Student Theses & Dissertations
Autologous stem cell therapy is a promising treatment for patients with diabetes worldwide. Previous stem cell-derived β (SC-β) cell protocols were unable to efficiently differentiate multiple patient induced pluripotent stem cells (iPSCs) into stem cell-derived islets (SC-islets), containing insulin-secreting SC-β cells. Recent updates targeting the actin cytoskeleton have enabled the differentiation of 14 diabetic and nondiabetic stem cell lines into SC-islets. We used genetic engineering, specifically CRISPR/Cas9, to correct the diabetes-causing mutation in stem cells from patients with Wolfram Syndrome. The genetically engineered SC-β cells functioned and had a composition similar to nondiabetic SC-β cells, unlike the unedited SC-β cells …
Contribution Of Tgf-B Signaling To The Pathogenesis Of Myeloproliferative Neoplasms, Juo-Chin Yao
Contribution Of Tgf-B Signaling To The Pathogenesis Of Myeloproliferative Neoplasms, Juo-Chin Yao
Arts & Sciences Graduate Student Theses and Dissertations
TGF-b expression is increased in most cases of myeloproliferative neoplasms (MPNs); however, its contribution to disease pathogenesis is not well understood. Here, we explore two specific hypotheses. First, we hypothesize that increased TGF-b signaling in mesenchymal stromal cells contributes to the development of myelofibrosis. Second, we hypothesize that Jak2 mutated hematopoietic stem cells (HSCs) are resistant to the growth suppressive effect of TGF-b, conferring a fitness advantage that contributes to their expansion in MPNs and clonal hematopoiesis. To test the first hypothesis, we abrogated TGF-b signaling in mesenchymal stem/progenitor cells by deleting Tgfbr2 using a doxycycline-repressible Osterix-Cre transgene (Osx-Cre), which …
Homeostatic T Cell Receptor Interactions With Self-Peptide Tune Cd4+ T Cell Function, Juliet Marie Bartleson
Homeostatic T Cell Receptor Interactions With Self-Peptide Tune Cd4+ T Cell Function, Juliet Marie Bartleson
Arts & Sciences Graduate Student Theses and Dissertations
Homeostatic T Cell Receptor Interactions with Self-Peptide Tune CD4+ T Cell FunctionbyJuliet Marie BartlesonDoctor of Philosophy in Biology and Biomedical SciencesImmunologyWashington University in St. Louis, 2021Professor Paul M. Allen, ChairMature 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 do not propagate canonical TCR activation pathways, …
Understanding The Molecular Mechanisms Of Photoferrotrophy And Phototrophic Extracellular Electron Uptake, Dinesh Gupta
Understanding The Molecular Mechanisms Of Photoferrotrophy And Phototrophic Extracellular Electron Uptake, Dinesh Gupta
Arts & Sciences Graduate Student Theses and Dissertations
Several anoxygenic phototrophs grow by utilizing soluble iron or insoluble mixed-valence iron minerals (such as rust) as electron donors to fix carbon dioxide using light energy, a process called photoferrotrophy. Photoferrotrophs can also use electron donors such as poised electrodes that serve as proxies for rust via phototrophic extracellular electron uptake (EEU). Despite the recognition that these two related microbial processes contribute to various biogeochemical cycles such as iron and carbon, the electron uptake mechanisms underlying photoferrotrophy and phototrophic EEU are poorly understood. To address the key knowledge gaps in our understanding of these microbial metabolisms, here we characterized Rhodopseudomonas …
The Role Of Mature Secretory Cells In Gastrointestinal Regeneration, Megan Deanna Radyk
The Role Of Mature Secretory Cells In Gastrointestinal Regeneration, Megan Deanna Radyk
Arts & Sciences Graduate Student Theses and Dissertations
Differentiated cells exhibit the ability to adjust their cell fate and become more progenitor-like after wide-scale tissue injury. This inherent cell plasticity is shown across many tissues and organisms and is a conserved behavior that ensures organ function even in a chronic injury setting. At the tissue level, the change in cell fate from a differentiated cell to one with more progenitor properties can be identified as metaplasia. Importantly, metaplasias, like Spasmolytic Polypeptide-Expressing Metaplasia (SPEM) in the stomach and Acinar-to-Ductal Metaplasia (ADM) in the pancreas, are risk factors for the development of adenocarcinoma. Thus, understanding the cellular and molecular mechanisms …
Genetics Of Pediatric Musculoskeletal Disorders, Lilian Antunes
Genetics Of Pediatric Musculoskeletal Disorders, Lilian Antunes
Arts & Sciences Graduate Student Theses and Dissertations
Pediatric musculoskeletal disorders are an extremely broad category of diseases that are often inherited. While individually rare, collectively these disorders are common, affecting around 3% of live births in the US. Despite the mounting clinical and molecular evidence for a genetic etiology, the cause for many patients with pediatric musculoskeletal disorders remain largely unknown. Major challenges in rare pediatric diseases include recruiting large numbers of patients and determining the significance and functional impacts of variants associated with disease within individuals or families. Whole exome sequencing (WES) is a powerful tool to identify coding variants that are associated with rare pediatric …
Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh
Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh
Arts & Sciences Graduate Student Theses and Dissertations
Stimulus-free brain dynamics form the basis of current knowledge concerning functional integration and segregation within the human brain. These relationships are typically described in terms of resting-state brain networks—regions which spontaneously coactivate. However, despite the interest in the anatomical mechanisms and biobehavioral correlates of stimulus-free brain dynamics, little is known regarding the relation between spontaneous brain dynamics and task-evoked activity. In particular, no computational framework has been previously proposed to unite spontaneous and task dynamics under a single, data-driven model. Model development in this domain will provide new insight regarding the mechanisms by which exogeneous stimuli and intrinsic neural circuitry …
Thermodynamics And Conformational Heterogeneity Of Recbcd Binding To Dna Ends, Linxuan Hao
Thermodynamics And Conformational Heterogeneity Of Recbcd Binding To Dna Ends, Linxuan Hao
Arts & Sciences Graduate Student Theses and Dissertations
E. coli RecBCD is crucial in initiating repair of double stranded (ds) DNA breaks. It is a heterotrimeric helicase and nuclease complex possessing two ATPase motors, RecB and RecD, and a regulatory subunit without ATPase activity, RecC. The RecB subunit also contains a 30kDa nuclease domain (RecBNuc) that, according to published structural data, is situated over 60Å away from the site of dsDNA binding. Surprisingly, we have shown in previous studies that deletion of RecBNuc to form RecBΔNucCD affects its dsDNA unwinding properties. The mechanism by which RecBNuc influences RecBCD dsDNA unwinding is unclear. In this thesis, equilibrium binding techniques, …
Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani
Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani
Arts & Sciences Graduate Student Theses and Dissertations
Complex microbial communities are at the interface of human, animal and environment interconnected ecosystem, where they can move within and between these entities. These microbial communities are mostly beneficial, maintaining the host health and homeostatic state. However, these communities can also serve as reservoirs of antibiotic resistance (AR) genes that may disseminate to pathogen bacteria, compromising the treatment options. Like other microbial communities, human gut microbiome is highly dynamic and can get acutely perturbed with the changes in the habitat, diet, lifestyle and disease. A perturbed gut community structure has profound impact on the host health and physiology. Use of …
Functional Interrogation Of Jak2 And Asxl1 Mutations In Myeloproliferative Neoplasms, Taylor Brost Collins
Functional Interrogation Of Jak2 And Asxl1 Mutations In Myeloproliferative Neoplasms, Taylor Brost Collins
Arts & Sciences Graduate Student Theses and Dissertations
JAK2 V617F is the most frequent mutation found in myeloproliferative neoplasms (MPNs), with 50-60% of myelofibrosis (MF) patients harboring this mutation. Mutations in ASXL1 often co-occur with JAK2 V617F and are associated with decreased survival and increased risk of transformation to secondary acute myeloid leukemia. How mutant ASXL1 contributes to the MPN disease phenotype and confers poor prognosis is not fully understood. Asxl1 mutation knock-in mouse models present with a relatively modest phenotype, following a long latency period and ASXL1 mutations have not been modeled in combination with JAK2 V617F. The field lacks human model systems that focus on how …
Ascension And Adhesion Of Uropathogenic Escherichia Coli During Pyelonephritis, Lisa Kristine Mclellan
Ascension And Adhesion Of Uropathogenic Escherichia Coli During Pyelonephritis, Lisa Kristine Mclellan
Arts & Sciences Graduate Student Theses and Dissertations
The ability of uropathogenic Escherichia coli (UPEC) to successfully establish an infection within the urinary tract relies on the pathogen to be able to navigate the complex interactions between pathogen and host. During a urinary tract infection (UTI), UPEC must ascend, adhere, and form bacterial communities in various infection niches, from the bladder (cystitis) to the kidneys (pyelonephritis). Each of these steps is critical for bacterial survival, and host and pathogen factors required at each stage can vary depending on host sex and anatomic niche. Preclinical modeling of pyelonephritis and sex effects on UTI has been limited due to the …
The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu
The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu
Arts & Sciences Graduate Student Theses and Dissertations
Proteases of the malaria parasite Plasmodium falciparum have been targeted for drug discovery for decades. The P. falciparum genome encodes ten aspartic proteases called plasmepsins, which are involved in diverse cellular processes. In this work we address the roles of two of these plasmepsins, plasmepsins IX and X (PM IX and X), the two least studied aspartic proteases in blood stage malaria parasites till date. We explore the essentiality of these proteases in parasite development, attempt to identify their substrates and the ability to drug them. We show that PM IX is essential for erythrocyte invasion, acting on rhoptry secretory …
Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath
Protein Synthesis Adaptation To The Au-Rich Transcriptome Of Plasmodium Falciparum, Jessey Lee Erath
Arts & Sciences Graduate Student Theses and Dissertations
The process of protein synthesis whereby a messenger RNA is decoded into an amino acid chainis conserved among the domains. Fastidious protein synthesis is necessary for organism survival. However, exceptions negatively affecting the mRNA translation cycle – inadvertently or by design – may occur. Polyadenosine tracts are one such motif causing ribosomal stalling and frameshifting in almost all organisms tested thus far; save Plasmodium spp. Thus, with ~60% of their protein-coding genome harboring polyadenosine tracts, the elucidation of such paradigm-breaking adaptations enabling Plasmodium spp. to translate this typically problematic motif without issue is salient from both basic science and clinical …
Prodrug Activation In Staphylococci And The Implications For Antimicrobial Development, Justin J. Miller
Prodrug Activation In Staphylococci And The Implications For Antimicrobial Development, Justin J. Miller
Arts & Sciences Graduate Student Theses and Dissertations
Antibiotic resistance is an increasing concern for global health care, with some estimates suggesting that 10 million people will die from antibiotic resistant infections in the year 2050. Fueling this prospect, few antimicrobials are being actively developed and recently commercial entities have fled from the development of new anti-infectives. New antimicrobials and drug development strategies are urgently needed to revitalize this critical pipeline. While many putative antibiotics demonstrate promising in vitro potency, they routinely fail in vivo due to poor drug-like properties (e.g. oral bioavailability, serum-half life, toxicity) resulting in overly expensive drug development pipelines. Fortunately, drug-like properties can be …
Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang
Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang
Arts & Sciences Graduate Student Theses and Dissertations
Human cancer is a complex and dynamic disease with mutational, spatial, and temporal heterogeneity. There has been a concerted effort to address the heterogeneity by profiling large-scale multiomic datasets with an emphasis on abnormalities such as DNA mutations at coding regions and structural variants. However, a systematic analysis of alterations at “dark matter” is lacking – including DNA slippage events at microsatellite sequences, gene fusions arising from genomic rearrangements, and aberrant DNA methylations at promoter regions. This dissertation focus on developing data-driven computational analysis pipelines to study the patterns of microsatellite instability, gene fusions, and aberrant DNA methylation, and their …
Investigating The Integration-Independent Role Of Hiv-1 In In The Viral Life Cycle, Jennifer Elliott
Investigating The Integration-Independent Role Of Hiv-1 In In The Viral Life Cycle, Jennifer Elliott
Arts & Sciences Graduate Student Theses and Dissertations
Human immunodeficiency virus type 1 (HIV-1) relies on a handful of essential enzymes for replication. Among these, the viral integrase enzyme (IN) plays a pivotal role in the viral life cycle by catalyzing the integration of the reverse-transcribed viral DNA into the host chromosome. While integration is the canonical role of IN, new research has uncovered an additional vital role for IN during virion morphogenesis. This dissertation elucidates how IN contributes to proper packaging of the viral RNA genome (vRNA) within the viral capsid and examines the fate of improperly formed viral particles in target cells.IN is proposed to mediate …
Targeting The Phgdh-Mtor Metabolic Axis In Osteosarcoma, Richa Rathore
Targeting The Phgdh-Mtor Metabolic Axis In Osteosarcoma, Richa Rathore
Arts & Sciences Graduate Student Theses and Dissertations
Altering cellular energy metabolism has been highlighted as one of the emerging hallmarks of cancer. The reprogramming of bioenergetic pathways towards enhanced glycolysis, rather than the mitochondrial oxidative phosphorylation indicative of normal cells, results in increased biomass production and is associated with the activation of various oncogenes. The increased or decreased expression of key metabolic enzymes has been identified as a potential family of biomarkers that could serve as the targets for novel metabolic-based therapies in cancer.The serine, glycine, and one-carbon (SGOC) metabolism pathway consists of a series of enzymes and metabolites that drive protein and lipid production, enhanced DNA …