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2021

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Exploring Contextual Differences In Environment And Policy Strategies To Promote Physical Activity In Disadvantaged Communities, Natalicio Hector Serrano Aug 2021

Exploring Contextual Differences In Environment And Policy Strategies To Promote Physical Activity In Disadvantaged Communities, Natalicio Hector Serrano

Arts & Sciences Graduate Student Theses and Dissertations

The benefits of physical activity for health are far reaching, including the reduced risk of several chronic diseases. However, only about 24% of US adults meet recommended guidelines of physical activity, with traditionally disadvantaged populations such as rural residents and persons of color facing even lower rates. Ecological models of health behavior help to understand correlates of physical activity that impact population health, but may not be as useful in disadvantaged populations where the evidence base is either lacking or not as rigorous. Furthermore, measures and methods may be underdeveloped in disadvantaged populations and there is a lack of understanding …

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Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim Aug 2021

Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim

Arts & Sciences Graduate Student Theses and Dissertations

The ability to discern gene expression at single cell level is revolutionizing our understanding of both basic biology and human health. Peripheral nerves are essential communicators between the outside world and the CNS, as evidenced by the devastating effects of diseases that disrupt them, such as ALS, Charcot-Marie-Tooth Syndrome and diabetic neuropathy. Understanding peripheral nerve dysfunction at a mechanistic level is of considerable interest due to the increasing prevalence and associated patient care costs of these disorders. Although most research of the peripheral nerve has focused on glial-axonal interactions, the important contributions of other cell types besides Schwann cells, such …

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Continuous-Time And Complex Growth Transforms For Analog Computing And Optimization, Oindrila Chatterjee Aug 2021

Continuous-Time And Complex Growth Transforms For Analog Computing And Optimization, Oindrila Chatterjee

McKelvey School of Engineering Graduate Student Theses & Dissertations

Analog computing is a promising and practical candidate for solving complex computational problems involving algebraic and differential equations. At the fundamental level, an analog computing framework can be viewed as a dynamical system that evolves following fundamental physical principles, like energy minimization, to solve a computing task. Additionally, conservation laws, such as conservation of charge, energy, or mass, provide a natural way to couple and constrain spatially separated variables. Taking a cue from these observations, in this dissertation, I have explored a novel dynamical system-based computing framework that exploits naturally occurring analog conservation constraints to solve a variety of optimization …

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Nucleation Studies In Barium Silicate Glasses And Soda-Lime Silicate Glass, Xinsheng Xia Aug 2021

Nucleation Studies In Barium Silicate Glasses And Soda-Lime Silicate Glass, Xinsheng Xia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Controlling nucleation is key for the manufacture of glasses and glass-ceramics. It has been observed by different researchers in many silicate glasses that at low temperatures the critical work of cluster formation (i.e. the nucleation barrier) slowly rises rather than decreasing with decreasing temperature. However, this experimental observation is in contradiction with nucleation theories. In this dissertation, crystal nucleation was studied in BaO·2SiO2, 5BaO·8SiO2, and Na2O·2CaO·3SiO2 glasses. The main research topics include measurements of the nucleation rate, the structural evolution of the glass, and the low-temperature nucleation behavior. A special focus is given to the low-temperature nucleation anomaly. In total, …

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Elucidating And Leveraging Dynamics-Function Relationships In Neural Circuits Through Modeling And Optimal Control, Sruti Mallik Aug 2021

Elucidating And Leveraging Dynamics-Function Relationships In Neural Circuits Through Modeling And Optimal Control, Sruti Mallik

McKelvey School of Engineering Graduate Student Theses & Dissertations

A fundamental research question in neuroscience pertains to understanding how neural networks through their activity encode and decode information. In this research, we build on methods from theoretical domains such as control theory, dynamical systems analysis and reinforcement learning to investigate such questions. Our objective is two-fold: first, to use methods from engineering to identify specific objectives that neural circuits might be optimizing through their spatiotemporal activity patterns, and second, to draw motivation from neuroscience to formulate new engineering principles such as synthesis of dynamical networks for decentralized control applications. We specifically take a top-down, optimization driven approach in our …

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Method Development For Enhancing Sensitivity Of Dynamic Nuclear Polarization Nuclear Magnetic Resonance Spectroscopy For Structural Studies Of Pkc-Drug Interactions, Patrick Terrence Judge Aug 2021

Method Development For Enhancing Sensitivity Of Dynamic Nuclear Polarization Nuclear Magnetic Resonance Spectroscopy For Structural Studies Of Pkc-Drug Interactions, Patrick Terrence Judge

Arts & Sciences Graduate Student Theses and Dissertations

To perform the most relevant structural studies on biological systems, experiments need to be carried out when the target proteins are in their endogenous cellular environment. Nuclear magnetic resonance (NMR) is well-suited to probe the structure and dynamics of a wide variety of systems, including biologically relevant proteins. However, NMR suffers from an inherent lack of sensitivity. Dynamic nuclear polarization (DNP) NMR is a powerful technique that is used to enhance NMR sensitivity by transferring the greater polarization of exogenously doped electron spins to nuclear spins of interest though the use of a high-power microwave source. Solid effect radicals offer …

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Regulation Of Transcription Factor Binding Specificity: From Binding Motifs To Local Dna Context, Jiayue Liu Aug 2021

Regulation Of Transcription Factor Binding Specificity: From Binding Motifs To Local Dna Context, Jiayue Liu

Arts & Sciences Graduate Student Theses and Dissertations

Regulation of transcription factor (TF) binding specificity lies at the heart of transcriptional control which governs how cells divide, differentiate, and respond to their environments. TFs are known to bind to DNA in a sequence specific manner, and such short sequence is known as transcription factor binding site (TFBS). However, the in vivo TF bound regions do not always contain a TFBS, and additionally, there are often excessive non-functional TFBSs with binding potential in the regulatory regions that are unbound for a given TF. This dissertation focuses on understanding the principles of TF binding specificity and is divided into two …

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Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu Aug 2021

Vestibulospinal Circuit In The Larval Zebrafish, Zhikai Liu

Arts & Sciences Graduate Student Theses and Dissertations

The vestibular system sense gravity and self-motion to help animals maintain body balance. Although vestibular signals inform the brain of the directions and speed of our body movements, it still remains unclear how these sensory information are processed and organized in the central nervous system. My thesis aims to illustrate neural computation underlying central vestibular tuning and the topographic organization of the vestibular circuits. First I established a novel approach to perform whole-cell recording of synaptic inputs in vivo during multi-axis movements in the central vestibular neurons. This technical advance allowed me to simultaneously measure presynaptic and postsynaptic tuning, along …

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Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell Aug 2021

Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell

Arts & Sciences Graduate Student Theses and Dissertations

The tumor suppressor TP53 (p53) is the most frequently mutated gene in cancer and among the most mutated genes in brain cancer. Functionally, p53 is a transcription factor that, when activated by an array of stress stimuli, regulates a complex transcriptional program that contributes to a variety of antiproliferative pathways. The loss of p53 function (LOF), either through mutation, deletion, or inhibition by alterations in the proteins that regulate p53, removes an essential barrier to the unfettered proliferation and genomic instability that drive transformation. Unlike most tumor suppressors, many p53 mutations are missense mutations that lead to stable expression of …

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Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell Aug 2021

Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …

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Neural Representation In The Primary Visual Cortex Amid High Neural Variability, Ji Xia Aug 2021

Neural Representation In The Primary Visual Cortex Amid High Neural Variability, Ji Xia

Arts & Sciences Graduate Student Theses and Dissertations

Animals process high-dimensional sensory information constantly. How does neural activityin sensory cortices represent this information? Recent advances in large-scale recordings allow us to monitor activity of hundreds or thousands of neurons simultaneously across a long period of time. Population recordings showed that cortical neuronal responses to repeated sensory stimulation is highly variable from trial to trial. However, how neurons in neocortex represent sensory information amid high neural variability is not well understood. To answer this question, we used two-photon calcium imaging to record from hundreds of excitatory neurons simultaneously from mouse primary visual cortex. We analyzed neural responses to repeated …

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Precision Diffusion Imaging To Analyze Individual-Specific Plasticity, Nicole Andrea Seider Aug 2021

Precision Diffusion Imaging To Analyze Individual-Specific Plasticity, Nicole Andrea Seider

Arts & Sciences Graduate Student Theses and Dissertations

Diffusion weighted imaging (DWI) is used to non-invasively infer and characterize the structure and integrity of the brain’s white matter fibers. Individual-specific precision diffusion imaging can identify additional organizational detail important for understanding basic brain connectivity and for advancing clinical applications of DWI in neuromodulation and neurosurgical planning. The reliability of individual specific DWI and data requirements for various analytic methodologies must first be systematically assessed. The reliability and accuracy of precision diffusion imaging was evaluated as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (Chapter 2). Parameter estimation methods that allowed …

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Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc Aug 2021

Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc

Arts & Sciences Graduate Student Theses and Dissertations

Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …

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The Evolving Mammalian 3d Epigenome, Mayank Choudhary Nishikant Choudhary Aug 2021

The Evolving Mammalian 3d Epigenome, Mayank Choudhary Nishikant Choudhary

Arts & Sciences Graduate Student Theses and Dissertations

One of life’s greatest mysteries is how a 6ft long-strand of DNA (our genome) fits inside the nucleus of a cell that’s less than a tenth of the width of a strand of hair. Adding to that, this genome has functioned faithfully with high fidelity over hundreds of millions of years of evolution is simply mind boggling. Moreover, within our genomes, we find millions of copies of strange genetic hitchhikers that were once thought to be purely self-seeking and parasitic. Critical advances in technology, assay development, sequencing, and computation have brought us today at an opportune moment in space and …

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Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy Aug 2021

Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy

Arts & Sciences Graduate Student Theses and Dissertations

The microtubule-binding protein tau is associated with neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and a subset of frontotemporal dementias. In these tauopathies, tau becomes hyperphosphorylated and forms intracellular neurofibrillary tau tangles, contributing to synaptic dysfunction, neuronal death, and severe astrogliosis. Tau can be classified as having a 3-repeat (3R) or 4-repeat (4R) structure, resulting from alternative splicing of exon 10 within the MAPT gene. While the higher deposition of 4R tau characterizes many primary tauopathies, the role of 4R tau in neurodegenerative disease pathogenesis remains unclear. To investigate the role of tau isoforms in disease, we created tau …

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Positron Emission Tomography From 1930 To 1990: The Epistemology And Process Of Scientific Instrumentation, Rick Shang Aug 2021

Positron Emission Tomography From 1930 To 1990: The Epistemology And Process Of Scientific Instrumentation, Rick Shang

Arts & Sciences Graduate Student Theses and Dissertations

Positron Emission Tomography (PET) is a groundbreaking detection system that, among many other applications, enabled neuroscience researchers to detect and image physiological changes in the brain associated with cognitive operations as subjects perform a task. This technology helped researchers learn to explore the physiological basis of human cognition in new ways and was the immediate forerunner of functional Magnetic Resonance Imaging (fMRI), a technology that continues to dominate the neurosciences. PET was also the founding invention of a new field of cognitive science: human functional neuroimaging. Indeed, some would say that PET encouraged a particular way of understanding the brain …

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C. Elegans Response To Cadmium Toxicity, Brian James Earley Aug 2021

C. Elegans Response To Cadmium Toxicity, Brian James Earley

Arts & Sciences Graduate Student Theses and Dissertations

Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. Residing in the same group of the periodic table, cadmium and zinc share chemical characteristics that are important for their industrial uses in electroplating, batteries, pigments, and metal alloys. The similarities of ionic cadmium and zinc have significant repercussions on biological systems. While it has long been clear that cadmium is toxic to biological systems, the mechanisms of cadmium toxicity remain poorly understood. In contrast, mechanisms of zinc homeostasis have been elucidated in growing detail. In C. elegans high zinc homeostasis is regulated …

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The Immunoregulation Of Autoimmune Diabetes, Hao Hu Aug 2021

The Immunoregulation Of Autoimmune Diabetes, Hao Hu

Arts & Sciences Graduate Student Theses and Dissertations

How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …

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Testing Janzen’S Physiological Barrier Hypothesis Through Experimental Evolution And Biogeographic Studies On Sister Species Pairs, Vincent John Fasanello Aug 2021

Testing Janzen’S Physiological Barrier Hypothesis Through Experimental Evolution And Biogeographic Studies On Sister Species Pairs, Vincent John Fasanello

Arts & Sciences Graduate Student Theses and Dissertations

Background: Janzen’s physiological barrier hypothesis suggests that variation in the effectiveness of physiological barriers to dispersal underlies global patterns of speciation and biodiversity. He noted that because a species’ physiology often evolves to match the range of conditions it has experienced in evolutionary history, it is likely that lineages that occupy habitats with wider ranges of temperature variation will tend to be better at dispersing across thermal gradients and will therefore be less likely to speciate as a result of mountain barriers. Despite decades of research into different aspects of this fundamental hypothesis, its assumptions and predictions remain largely untested.Methods: …

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The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse Aug 2021

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

Arts & Sciences Graduate Student 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 …

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The Evolutionary History Of Camelina Crantz (Brassicaceae) And Domestication Of The Biofuel Crop, C. Sativa (L.) Crantz, Jordan Brock Aug 2021

The Evolutionary History Of Camelina Crantz (Brassicaceae) And Domestication Of The Biofuel Crop, C. Sativa (L.) Crantz, Jordan Brock

Arts & Sciences Graduate Student Theses and Dissertations

The mustard family, Brassicaceae, is a large and economically important group of plants comprising ~350 genera and ~4060 species. Within the family, one genus, Camelina, has been neglected and nearly forgotten until recent decades. This genus comprises between 7 – 9 species, and includes Camelina sativa, an ancient oilseed crop cultivated for thousands of years in Europe. An allohexaploid, C. sativa contains high levels of omega-3 fatty acids and a seed oil composition amenable for production of aviation jet fuel. With a short generation time and ability to be cultivated on marginal soils with few inputs, C. sativa is set …

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The Role Of Excited States In Determining Β-Lactamase Function And Bacterial Fitness, Catherine Rae Knoverek Aug 2021

The Role Of Excited States In Determining Β-Lactamase Function And Bacterial Fitness, Catherine Rae Knoverek

Arts & Sciences Graduate Student Theses and Dissertations

Proteins are macromolecular machines that play a role in nearly every biological process. They are dynamic molecules which adopt many different conformations as they fold into their 3D structures, interact with their binding partners, and perform their functions. The most probable (lowest energy) protein conformation is referred to as the ground state, and this is often assumed to be the state determined by experimental methods such as x-ray crystallography. However, proteins also adopt higher energy excited states which can have significant probabilities. As these excited states are notoriously difficult to find and study, it is unclear if excited states contribute …

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Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek Aug 2021

Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek

Arts & Sciences Graduate Student Theses and Dissertations

Pain and opioid use disorder prevalence, diagnoses of mental health disorders, and rate of suicide have all skyrocketed over the last 30 years as a matrix of public health crises. Each reduces quality of life and installs risk of the others; together, they have burdened our country with nearly unmanageable healthcare challenges. Although the critical demand for novel and more effective therapeutics has been clear for decades, relatively little progress has been made to address pain and its comorbidities. Repeated clinical trial failures have called into question the preclinical evidence upon which they are based. Preclinical models of pain-induced negative …

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Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker Aug 2021

Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker

Arts & Sciences Graduate Student Theses and Dissertations

People with chronic LBP display an altered movement pattern where the lumbar spine moves more readily than other joints that can contribute to the activity. The pattern is of particular clinical relevance because across multiple studies the magnitude of altered pattern is associated with LBP and function. One session of motor skill training (MST) during functional activities can improve the altered pattern. However, of the few studies investigating MST for people with LBP, none have examined the short-term or long-term effects of MST on the altered pattern. Additionally, no study has systematically examined if person-specific characteristics moderate the altered pattern …

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Association Of Structural Variation (Sv) With Cardiometabolic Traits In Finns, Lei Chen Aug 2021

Association Of Structural Variation (Sv) With Cardiometabolic Traits In Finns, Lei Chen

Arts & Sciences Graduate Student Theses and Dissertations

Cardiovascular diseases (CVDs) are known to be associated with a variety of quantitative risk factors such as cholesterol, metabolites, and insulin. Understanding the genetic basis of these quantitative traits can shed light on the etiology, prevention, diagnosis, and treatment of disease. However most prior trait-mapping studies have focused on single nucleotide variants (SNVs) and Indels, with the contribution of structural variation (SV) remaining unknown. In this thesis, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. In the first chapter, we used sensitive methods to identify and genotype 129,166 high-confidence …

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Dendritic Processing And Efficient Coding In The Retina, Jen-Chun Hsiang Aug 2021

Dendritic Processing And Efficient Coding In The Retina, Jen-Chun Hsiang

Arts & Sciences Graduate Student Theses and Dissertations

In early sensory systems, a copious amount of information needs to be simultaneously processed to extract salient stimulus features and compress representations for efficient transmission. My thesis addresses how the retina processes visual information to detect specific motion patterns and efficiently encode our environment for perception. Around 40 retinal ganglion cell (RGC) types in mammals send specific feature representations through their axons from the retina to the brain. RGCs are the sole source of visual information to the brain. Recent studies suggest that amacrine cells (ACs) generate feature-selective responses of RGCs, but little is known about their neuronal computations. We …

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Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda Aug 2021

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Graduate Student Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

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Testing Candidate Cerebellar Presymptomatic Biomarkers For Autism Spectrum Disorder, Zoe Wilson Hawks Aug 2021

Testing Candidate Cerebellar Presymptomatic Biomarkers For Autism Spectrum Disorder, Zoe Wilson Hawks

Arts & Sciences Graduate Student Theses and Dissertations

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed on the basis of social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar-mediated error signaling impairments contribute to the causation of ASD. However, the relationship between infant cerebellar functional connectivity (fcMRI) and later ASD behaviors and outcomes has not been investigated. Such work is critical to establish early (presymptomatic) cerebellar correlates of ASD. Methods: Data from the Infant Brain Imaging Study (n=94, 68 male) were used to evaluate cerebellar fcMRI as a presymptomatic biomarker for ASD. Specifically, brain-behavior associations were analyzed for 6-month cerebellar connections in relation …

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Copper-Mediated Regulation Of A Traditional Iron Uptake System In Uropathogenic Escherichia Coli., George Lwanga Katumba Aug 2021

Copper-Mediated Regulation Of A Traditional Iron Uptake System In Uropathogenic Escherichia Coli., George Lwanga Katumba

Arts & Sciences Graduate Student Theses and Dissertations

Transition metals constitute an important part of the host-pathogen interface. Iron is an essential nutrient that functions as a cofactor for numerous bacterial and host proteins, as either a ligand for oxygen in carrier proteins or an enzyme catalytic site due to its natural redox properties. As part of the innate immune response, infected hosts sequester iron from pathogens to limit their growth, a phenomenon known as nutritional immunity. On the other hand, copper ions are deployed at infection sites as a potent antimicrobial agent to kill bacteria. The ability to survive within multiple, often harsh, microenvironments is fundamental to …

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Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster Aug 2021

Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster

Arts & Sciences Graduate Student Theses and Dissertations

Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …

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