Life Sciences Commons^™

Employing Ai To Enhance In-Class Role Playing Scenarios, Eric Fournier

Generative AI Teaching Activities

Role playing can deepen student’s engagement with course content and help them develop skills while learning course material. Students will use AI to develop their characters and help them craft compelling arguments in the role-play scenarios

Teaching Evolutionary Principles With Ai Image Generators, Jacqueline Garnett

Generative AI Teaching Activities

The purpose of this assignment is for students to practice constructing phylogenies using the principle of parsimony. In this activity, students will use an AI Image Generator to create a grid of images of the same organism and identify a series of traits that vary to build a possible phylogenetic tree.

Biology Department Publications: 2023, Sam Lindgren

Biology Department Bibliographies

This document is a non-comprehensive list of publications made by graduate students, post-doctoral researchers, and faculty members in the Biology Department in 2023. It indexes those publications available through PubMed and Scopus, and serves as an archival record of the Department’s robust scholarly contributions.

Uvrd1 Helicase Of Mycobacterium Tuberculosis That Can Be Activated By Multiple Unique Mechanisms, Ankita Chadda

Arts & Sciences Electronic Theses and Dissertations

Abstract Mycobacterium tuberculosis (Mtb) causes tuberculosis disease in humans and is one of the leading causes of death worldwide due to infectious agents. During infection, Mtb is exposed to reactive oxygen species and reactive nitrogen intermediates from the host immune response that causes DNA damage. UvrD-like helicases are involved in DNA repair and use energy from ATP hydrolysis to translocate on single stranded DNA (ssDNA) or unwind double-stranded DNA (dsDNA) to remove the damaged DNA strand. Previous studies on UvrD-like helicases have shown that they exist in a monomer-dimer equilibrium and unwind only as dimers in the absence of accessory …

The Evolution Of Transposable Elements As Cis-Regulatory Elements In Mammals, Alan Y. Du

Arts & Sciences Electronic Theses and Dissertations

Transposable elements (TEs) are mobile genetic elements that make up a large proportion of mammalian genomes. Although TEs are highly prevalent genomic sequences, they have been understudied as they were once labeled as “junk DNA.” Despite their initial status as simple genomic parasites, recent studies have implicated TEs as cis-regulatory elements, supplying promoters, enhancers, and boundary elements. Functional testing of regulatory activity, however, remains a significant bottleneck. Nonetheless, due to their repetitive nature, TEs provide a unique model to examine the evolution of cis-regulatory elements, which has traditionally been difficult to study due to lack of homology at the sequence …

Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen

McKelvey School of Engineering Theses & Dissertations

Protein Kinase A (PKA) plays important roles in diverse biological processes such as sleep, long term memory, and synaptic plasticity. In addition, PKA also acts as an integrator of neuromodulator signaling though G protein-coupled receptor activation. However, despite genetic knockout and pharmacological inhibition experiments that demonstrate the importance of PKA, it is unclear where, when, or how PKA plays these roles in cellular physiology and behavior. In order to better understand the function of PKA in these processes, and how neuromodulator signaling drives complex behavioral changes, there exists a need for a method to selectively activate/inactivate PKA with high spatial …

Manage Your Money Wisely: How Consumers And Marketers Can Effectively Communicate Money Issues, Alexander Park

Olin Business School Electronic Theses and Dissertations

Consumers and marketers find it challenging to communicate money matters. For example, consumers experience discomfort and uneasiness when discussing financial issues with their social relationships. Firms often receive backlash when sharing their good financial deeds (e.g., charitable efforts) with consumers. Because financial matters can be a sensitive topic, in my research, I explore the difficulties consumers and marketers experience when communicating money issues and how they can better navigate these problems.In Chapter One, I investigate a particularly uneasy interaction that consumers often face with their friends and acquaintances: the need to ask for money back. Seven fully preregistered studies (N …

Single-Molecule Super-Resolution Imaging Of Geobacter Sulfurreducens Under Anaerobic Conditions, Ziyi Hu

McKelvey School of Engineering Theses & Dissertations

Geobacter sulfurreducens are anaerobic bacteria capable of making electrical contacts with other organisms and extracellular electron acceptors. The challenge of imaging live Geobacter bacteria is maintaining anaerobic conditions during the imaging process. In this thesis, we augment a single-molecule localization microscope (SMLM) with a home-built anaerobic imaging chamber and use constant argon bubbling to maintain oxygen-free imaging conditions. To validate the imaging protocol, we use the transient binding of Nile red to resolve the spherical morphology of lipid-coated glass spheres with nanoscale resolution. However, when imaging Geobacter, the distribution of Nile red localizations is non-uniform, both between different cells …

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

Elsewhere: In Defense Of Daydreaming, Alex Braden

MFA in Visual Art

Much like music, organic life is an absurd, improbable, and serendipitous instance. I set circular, electric, acoustic, and magnetic forces in motion and allow them to coalesce freely in the hopes of synthesizing unexpected moments of beauty, connection, and harmony.

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park

McKelvey School of Engineering Theses & Dissertations

Gastrulation is an early morphogenetic process that is conserved across most metazoans and lays out the future body plan through the formation and shaping of the three germ layers: endoderm, mesoderm, and ectoderm. Despite its importance, not much is known about the events surrounding human gastrulation that occurs in utero due to ethical and technical limitations on studying human embryos. Therefore, many researchers have devised protocols for creating in vitro models of gastrulation using embryonic stem cells. Initially starting with mouse embryonic stem cells, the field of in vitro embryo models has advanced rapidly, with protocols using human embryonic stem …

Bioinformatics And Cancer Genomics Approaches To Advance Precision Medicine And Elucidate Tumor Mutational Landscapes, Kelsy Cotto

Arts & Sciences Electronic Theses and Dissertations

Next-generation sequencing of DNA and RNA continues to be integrated into pre-clinical and clinical research. However, challenges still remain that impede the translation of findings into an improved understanding of human diseases or clinically actionable alterations. The projects described in this dissertation start with compiling efforts from experts who have identified druggable genes within the human genome, followed by in-depth analyses which characterize the pan-cancer landscape of splice-associated mutations and noncoding, regulatory mutations across multiple subtypes of breast cancer. In Chapters 2 and 3, substantial efforts were made to update the content and the user experience for the drug-gene interaction …

A Universal Mechanism Of G Protein Inhibition, Tyson Daniel Todd

Arts & Sciences Electronic Theses and Dissertations

G protein coupled receptors transduce a truly staggering number of diverse extracellular signals including chemical messengers, physical force, and even photons into specific cellular responses through their coupling to heterotrimeric G proteins. G proteins amplify the originating signal through their binding to downstream effectors, activating a complex network of overlapping responses that allow the cell to respond perfectly to that specific stimulus. It is critical to the cell that this process is carried out faithfully in order to respond to the myriad environmental cues and avoid injury, exhaustion, and death for the individual cell or the development of pathology if …

Insights Into The Non-Osmoregulatory Function Of A Pollen-Specific Mechanosensitive Ion Channel, Kari Miller

Arts & Sciences Electronic Theses and Dissertations

Pollen, the male gametophyte of flowering plants, delivers the sperm cells to the ovule to carry out sexual reproduction. During this process, the pollen grain undergoes dramatic physical changes. Survival requires careful control of cell mechanics, particularly the balance between protoplast expansion and cell wall resistance. One control mechanism is the use of a mechanosensitive (MS) ion channel, MscS-Like (MSL)8. This pollen-specific protein was previously shown to be essential for pollen survival during hydration and was proposed to function as a tension-gated osmoregulator. However, direct proof of osmoregulation during initial hydration has not yet been found. In fact, studies of …

A Structural Perspective On Neutralizing Antibodies To Flaviviruses And Coronaviruses, John Michael Errico

Arts & Sciences Electronic Theses and Dissertations

The presence of neutralizing antibodies typically correlates strongly with protection from infection, particularly for RNA viruses; elicitation of neutralizing antibody responses is thus the primary goal of most vaccines, and monoclonal antibodies (mAbs) can be leveraged as potent therapeutics. Thus, understanding the properties of individual antibodies that comprise polyclonal antibody responses and their epitopes is essential for countermeasure design. In this dissertation, I explore the epitopes and functional properties of monoclonal antibodies targeting the structural proteins of two families of RNA viruses, flaviviruses and coronaviruses.

Flaviviruses are globally distributed arthropod-borne positive-sense RNA viruses transmitted primarily by either mosquitos or ticks. …

Connections Between Mechanosensitive Ion Channel Msl10 And Er-Plasma Membrane Contact Sites, Jennette Marie Codjoe

Arts & Sciences Electronic Theses and Dissertations

Mechanosensitive (MS) ion channels are an evolutionarily conserved way for cells to sense mechanical forces and transduce them into ionic signals. A plasma membrane-localized MS channel from Arabidopsis thaliana, MscS-Like (MSL)10, senses cell swelling and initiates a signaling cascade that triggers programmed cell death. Whereas the channel properties of MSL10 have been well studied, how MSL10 signals remains largely unknown. I worked collaboratively to show that important lesions for cell death signaling in the cytosolic N- and C-terminal domains of MSL10 interact genetically. I also helped show that ionic flux through MSL10 is dispensable for signaling, which suggested that MSL10 …

Understanding Gene Regulation With High-Throughput Genome-Integrated Reporter Assays, Clarice Hong

Arts & Sciences Electronic Theses and Dissertations

Proper spatiotemporal gene expression depends on specific interactions between cis-regulatory sequences (CRSs) and chromatin modifications at a genomic location. However, we do not yet understand the rules that determine how CRSs work together to influence gene expression. The goal of this thesis is to systematically assay and quantify how different genomic environments interact with CRSs to control gene expression output using a variety of genome-integrated massively parallel reporter assays (MPRAs). First, we tested the hypothesis that core promoters confer specificity by only responding to compatible enhancers and chromatin in specific genomic environments. We measured the activities of hundreds of core …

Generation, Characterization, And Treatment Of Functional Zebrafish Models For Musculoskeletal Disorders, Julia Nicole Whittle

Arts & Sciences Electronic Theses and Dissertations

Musculoskeletal disorders in humans present with a broad range of phenotypes that vary in severity, onset, and genetic cause. The musculoskeletal system is comprised of complex and diverse tissues that make up the majority of total body mass. Thus, mutations in many different genes with differing structure and function can produce phenotypically similar developmental and morphological defects in the muscle and skeleton. In addition, the muscular and skeletal systems develop non-autonomously, wherein development and function of each will affect development of the other. Thus, mutations in genes responsible for development of this complex system have the potential to influence morphogenesis …

Using Proteomics To Discover New Connections In The Arabidopsis Circadian Clock, Maria Lynn Sorkin

Arts & Sciences Electronic Theses and Dissertations

The plant circadian clock is an endogenous timekeeping mechanism that uses daylength and temperature cycles to synchronize internal physiology with the external environment. Much of our understanding of the clock in the model plant Arabidopsis thaliana comes from genetic approaches. In this thesis, I use affinity purification coupled with mass spectrometry (APMS) to identify protein-protein interactions for core clock components on a proteomic scale. I developed and optimized a protocol to perform APMS on a core set of circadian clock proteins: CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), LATE ELONGATED HYPOCOTYL (LHY), PSEUDORESPONSE REGULATOR 5 (PRR5), PRR7, PRR9, TIMING OF CAB 1 …

Roles Of Behavioral Novelty And Organismal Energetics In The Evolution Of Extreme Encephalization, Erika Laurie Schumacher

Arts & Sciences Electronic Theses and Dissertations

Brains and their component brain regions vary widely in size and structure across vertebrates. However, extreme increases in total brain size relative to body size (extreme encephalization) and increases in specific major brain region sizes independent of other brain regions (mosaic brain evolution) are relatively rare. There are several hypotheses as to why, but the energetic cost of increased brain tissue and the regional interconnectedness in both brain development and function likely constrain how brains are able to change in response to selection. In this dissertation, I sought to address both how behavioral novelty relates to evolutionary changes in brain …

Dysregulation Of Gene Expression In Non-Photosensitive Trichothiodystrophy, Brittany Townley

Arts & Sciences Electronic Theses and Dissertations

The pre-mRNA life cycle requires intron processing; yet, how intron processing defects influence splicing and gene expression is unclear. Here, we find TTDN1, which is frequently mutated in non-photosensitive trichothiodystrophy (NP-TTD), functionally links intron lariat processing to the spliceosome. The conserved TTDN1 C-terminal region directly binds lariat debranching enzyme DBR1, while its N-terminal intrinsically disordered region (IDR) binds the intron binding complex (IBC). The IDR forms condensates in vitro and is needed for IBC interaction. TTDN1 loss causes significant intron lariat accumulation, as well as splicing and gene expression defects, mirroring phenotypes observed in NP-TTD patient cells. Ttdn1∆/∆ mice recapitulate …

Mechanisms For High Light Tolerance In A Fast-Growing Cyanobacterium, Patricia Walker

Arts & Sciences Electronic Theses and Dissertations

Through oxygenic photosynthesis, cyanobacteria, algae, and plants convert light into chemical energy. However, highly energetic light often damages the photosynthetic apparatus, which can lead to the decline of photosynthetic activity (photoinhibition), and prolonged photoinhibition can lead to cell death. Cyanobacteria enact various protective mechanisms to mitigate photodamage, many of which have been conserved in plants. Repair of PSII reaction centers, decreased light absorption, quenching of excess absorbed energy, and biosynthesis of antioxidants all work to mitigate damage during high light. Due to the adjustments to photosynthesis, acclimation to high light requires remodeling of cellular metabolism and physiology. Therefore, phototrophs have …

Canonical And Noncanonical Mechanisms Of Resistance To Arginine Starvation In Cancer, Leonard Christopher Rogers

Arts & Sciences Electronic Theses and Dissertations

The enzyme argininosuccinate synthetase 1 (ASS1) catalyzes the condensation of citrulline and aspartate into argininosuccinate as part of the urea cycle and citrulline-nitric oxide cycle. This reaction is essential for mammals to synthesize the amino acid arginine, which is required for all cells. Nearly all human tissues express at least some ASS1, but they import most of their arginine from the extracellular space after it is produced and released by the kidneys. Most solid tumors lack a functional level of ASS1, including over 85% of sarcomas, which are cancers of connective tissues. Published evidence suggests that this provides a proliferation …

Characterizing Complex Affective Processing Across Age And In Relation To Social Anxiety Symptoms, M. Catalina Camacho

Arts & Sciences Electronic Theses and Dissertations

Humans require a shared understanding of others’ emotions for adaptive social functioning. For instance, if someone tells a joke and another person laughs, we assume the laughing person was happy because we have a shared concept for such positive interactions. Children develop and refine these concepts as they grow up, but the underlying neural processing that supports this development is unknown. Identifying the neurodevelopment underlying emotion processing could provide important insight to emotional disorders. For example, social anxiety is associated differences in the detection and interpretation of negative or neutral emotional cues, but the underlying neurodevelopment of this behavior is …

Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer

Arts & Sciences Electronic Theses and Dissertations

The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …

The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen

Arts & Sciences Electronic Theses and Dissertations

Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …

Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy

Arts & Sciences Electronic Theses and Dissertations

Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …

Analyzing The Interconnectedness Of The Human Genome, Nicholas Jacobs

Arts & Sciences Electronic Theses and Dissertations

The human genome is much more interconnected than many people realize. In this thesis, I will outline two efforts to portray this idea. First, I will seek to display that cell fitness is an omniphenotype. That is to say, cell fitness can be used to determine whether an unknown factor interacts with a known factor for any phenotype. The human genome is sufficiently interconnected that if two factors interact with one another then that can be reflected by a multiplicative change in cell fitness. This change in fitness can be used to determine if a new factor of interest is …

The Enemy Within: An Investigation Of The Intracellular Bacteria In Urinary Tract Infections, Jennie Elizabeth Hazen

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTIs) are common diseases that are associated with significant morbidities. Multiple studies have indicated that multiple species of uropathogenesis bacteria invade and persist within bladder epithelial cells as a necessary step of uropathogenesis. Interestingly, many of these species are not canonically associated with intracellular infections. Although the first study describing bacteria within the urothelium was published two decades ago, this critical step of uropathogenesis remains relatively understudied.

I established a murine model of community-acquired A. baumannii UTI, a previously unstudied manifestation of the disease. While immunocompetent mice resolved their infections quickly, immunocompromised mice displayed high bacterial burdens …

Inferring Adaptation In Social Microbes From Experimental Evolution Under Relaxed Selection, Tyler John Larsen

Arts & Sciences Electronic Theses and Dissertations

Microbes exist against a backdrop of other organisms, and the interactions between microbes have major consequences on their traits, their evolution, and their impact on the world. Microbial interactions and the adaptations that enable them are extremely diverse – they can unlock abilities beyond the reach of individual cells or lead to a population’s destruction, they can be temporary or permanent, they can be between genetically identical cells or different species entirely. The first chapter of this dissertation reviews microbial interactions and the related concept of the evolution of conflict and cooperation.To be certain a trait is an adaptation at …