Biology Commons^™

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.

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 …

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 …

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 …

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 …

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 …

Tfa Inference: Using Mathematical Modeling Of Gene Expression Data To Infer The Activity Of Transcription Factors, Cynthia Ma

McKelvey School of Engineering Theses & Dissertations

Transcription factors (TFs) are a set of proteins that play a key role in the information processing system that enables a cell to respond to changes in internal and external state. By binding near a gene in a cell’s DNA, a TF can influence that gene’s expression level, triggering the appropriate increase or decrease in production levels of proteins that are needed to handle stressors like a change in nutrient availability or damage to the cell’s internal structures. Transcription factor activity (TFA) is a measure of how much effect a TF has on its target genes in a given sample …

Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough

Arts & Sciences Electronic Theses and Dissertations

The overall goal of this dissertation is to gain a better understanding of how current Alzheimer disease pathologic progression models interact with sources of individual-level variation in pathology to influence overall disease progression in a clinically meaningful way. Many sources of variation, both internal (e.g., genetic mutations, heterogeneity of tau pathology) and external (e.g., diet and exercise, sleep quality), are known to influence disease progression and symptom onset in AD. With the advent of therapies that have shown successful reduction of amyloid load in trials and the rapid progression of anti-tau therapies, we hypothesize that a better understanding of how …

Antigen Presentation In Central Nervous System Antitumor Immunity, Jay Aaron Bowman-Kirigin

Arts & Sciences Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) patients face limited treatment options and poor outcomes. The median survival is less than two years, and there are no FDA approved immune therapies. Although GBM itself is an immune-suppressive, heterogeneous tumor, the lack of FDA approved immune therapies might be in part because the cancer immunity cycle is less well understood for GBM than for other tumor types. My studies focused on developing mouse models of malignant glioma that more faithfully recapitulate human GBM from an immunologic perspective, and on defining the role of the conventional dendritic cell 1 subset (cDC1) and lymphatic drainage in central …

Techniques For Spatial Analysis Of C. Elegans Anatomy And Reporter Expression, Nicolette Marie Laird

Arts & Sciences Electronic Theses and Dissertations

Quantitative analysis of microscopy images is integral to investigating biological phenomena. Despite a variety of tools to aid in analyzing C. elegans images, quantitative microscopy studies are still difficult due to the flexible and deformable nature of the nematode. These differences in posture and shape must first be corrected before analysis. Manual approaches to solve these problems are time intensive and infeasible for large datasets. Additionally, current automated tools rely on high-magnification imaging using labeled nuclei as fixed markers for comparison. Labelling can be achieved either with transgenic animals or fluorescent dyes; however, both of these can be impractical for …

Macrophage Proliferation Machinery Drives Immunosuppression And Pdac Progression (巨噬细胞增值机制抑制肿瘤免疫促进胰腺癌发展), Chong Zuo

Arts & Sciences Electronic Theses and Dissertations

Tumor-associated macrophages (TAMs) are abundant in near all solid tumors and are involved in many aspects of cancer progression. The presence of TAMs is negative prognostic indicator in several cancer types including pancreatic cancer. Attempts to target this population by limiting their number in PDAC tumors have not achieved promising results, as compensatory resistance pathways have already been defined. The heterogeneity of TAMs puts another barrier into this targeting strategy, given macrophage subsets are important in maintaining tissue homeostasis and some in performing anti-tumor functions. Previous studies have shown that TAMs in PDAC tumors have dual origins – HSC-derived and …

The Maintenance Of Cd4 And Cd8 T Cell Response To Persistent Antigens, Yu Xia

Arts & Sciences Electronic Theses and Dissertations

In response to transient antigen presence in the context of acute infections or vaccinations, antigen-specific naïve T cells clonally expand and differentiate. Most of the expanded cells undergo terminally differentiation and die following antigen clearance to re-establish immune homeostasis. In contrast, when the pathogen persists, such as in the context of chronic viral infections or anti-tumor immunity, while T cells undergo alternative differentiation known as exhaustion due to their reduced functionality, T cells still contribute to pathogen control and its response is sustained for longer duration due to unknown mechanisms. The goal of my thesis work is to understand how …

Determinants Of Dna Damage Responses During B Cell Development, Rachel Leigh Johnston

Arts & Sciences Electronic Theses and Dissertations

Cellular DNA is regularly threatened by both physiologic (normal cellular mechanisms) and genotoxic (external exposures, such as irradiation and chemotherapy) insults. DNA double- stranded breaks (DSBs) are the greatest risk to the genome as they present opportunities for errant repair as mutations or translocations. To minimize these risks, DSBs activate highly conserved signaling pathways to coordinate cell cycle arrest, cell death and DNA repair. During normal development, B cells intentionally create site-specific chromosomal DSBs to assemble the immunoglobulin receptor (Ig) genes necessary for specific responses to pathogens. These programmed DNA breaks are generated by the recombinase activating gene (RAG) complex, …

Multi-Omics Investigation Of Tumor Heterogeneity, Oncogenic Signaling, And Treatment Response In Human Cancers, Yige Wu

Arts & Sciences Electronic Theses and Dissertations

Cancer is a highly complex disease with aberrations at the genetic, epigenetic, transcriptomic, and protein levels that drove its phenotypic diversity. Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, comprising roughly 80% of cases. To define the epigenetic and transcriptomic regulation of ccRCC at the single nucleus (sn) level, we performed snRNA-seq and snATAC-seq in 34 and 28 samples respectively, including primary tumors and normal adjacent tissues, and matched them with bulk proteogenomics data. We identified tumor-specific markers and tumor subpopulations using snRNA-seq, which demonstrated diverse pathway activity within and across patients. PBRM1 and …

Overcoming Genetic Heterogeneity In Glioblastoma By Targeting Transcriptional Dependencies, Tatenda Mahlokozera

Arts & Sciences Electronic Theses and Dissertations

Glioblastoma (GBM) is the most common intrinsic central nervous system malignancy in adults, accounting for approximately 45% of such cancers. Despite advances in chemo- and radiotherapeutic approaches for various malignancies over the past decade, GBM remains an incurable disease with a dismal prognosis. Even after treatment with the current standard of care, which consists of maximal safe surgical resection, radiotherapy, and both concomitant and adjuvant chemotherapy with temozolomide, median survival is only approximately 17 months. Both treatment failure and difficulties in developing novel targeted therapies for GBM have partly been attributed to the molecular and cellular inter- and intra-tumoral heterogeneity …

T Cell Regulation Of Regenerative Environment In Acellular Nerve Allograft Repaired Peripheral Nerves, Deng Pan

Arts & Sciences Electronic Theses and Dissertations

Peripheral nerve injury (PNI) is common and has debilitating long term sequelae. Development of new therapies to improve regeneration following PNI is therefore critical. Acellular nerve allografts (ANAs) are increasingly utilized in the clinic for the repair of PNI and an improved mechanistic understanding of nerve regeneration through ANA is important for developing better therapies. Inflammation is an important aspect of regeneration, and the role of macrophage has been increasingly documented. Other aspect of inflammation has not been well-defined. In particular, there is limited understanding on the role of T cells in the regeneration of peripheral nerve. However, evidence in …

Sex Differences In Cancer Metabolism Contribute To Sex-Specific Treatment Responses, Jasmin Inge Sponagel

Arts & Sciences Electronic Theses and Dissertations

Many human diseases show sex differences in incidence, age of onset, and outcome, including autoimmune diseases, neurological diseases, psychiatric disorders, cardiovascular diseases, metabolic diseases, neurodevelopmental disorders, and cancer. For most cancers, incidence and mortality rates are higher in males. Lung and brain cancers are no exception. Overall, lung cancer is more common in males. Furthermore, mortality rates of non-small cell lung cancer (NSCLC), the most common subtype of lung cancer, are significantly higher in males. The underlying reasons for sex differences in NSCLC mortality rates are largely unknown. Most brain cancers are also more common in males. The male prevalence …

Regulation Of Metabolic Stress By The Snhg3 Locus, Arthur Curtis Sletten

Arts & Sciences Electronic Theses and Dissertations

Dyslipidemia and lipotoxicity are pathologic signatures of the metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not fully understood. To identify novel genes involved in metabolic stress, our group performed an unbiased forward genetic screen for lipotoxicity resistance. My studies focused on characterizing one of the mutant cell lines isolated from this screen, in which promoter trap mutagenesis disrupted one allele of the small nucleolar RNA hosting gene 3 (Snhg3).

I demonstrate that diminished expression …

Developments In Proteomics, Trans-Splicing Technology And Endogenous Transcript Manipulation, Justin Alexander Melendez

Arts & Sciences Electronic Theses and Dissertations

Technological innovation drives scientific discovery, unlocks new avenues of research, and allows us to ask questions in ways that were previously unavailable. With each technological advance, our ability to perturb and explore biological systems has grown in ways previously unimagined. The theme of my thesis is the development of new technologies in biology. To this end, I have worked on three technologies that contribute to the areas of protein sequencing, RNA barcoding for trans-splicing and single-cell applications, and a new method for transcriptional knockdown.

In my first project, digital analysis of proteins by end sequencing (DAPES), we set out to …

Regional Reprogramming And The Small Intestine: Analysis And Modeling Of Adaptive Regeneration Of The Epithelium, Sarah Elizabeth Waye

Arts & Sciences Electronic Theses and Dissertations

The small intestine in homeostasis is capable of regular regeneration, but in cases of massive injury like Short Bowel Syndrome, the innate human response often fails to fully compensate for the loss of nutrient absorptive surface area that accompanies bowel resection. Murine models display an active compensatory reaction deemed “adaptation” in which the surface area of the bowel is increased to accommodate nutrient absorptive needs. This observation has highlighted several gaps in knowledge regarding bowel adaptation. Firstly, what occurs on a molecular level in murine models during adaptation? Secondly, how can the findings in mice be applied to humans in …

Chemical Damage To Mrna And Its Impact On Ribosome Quality-Control And Stress-Response Pathways In Eukaryotic Cells, Liewei Yan

Arts & Sciences Electronic Theses and Dissertations

Ribosome often faces defective adducts that disrupt its movement along the mRNA template. These adducts are primarily caused by chemical damage to mRNA and are highly detrimental to the decoding process on the ribosome. Hence, unless dealt with, chemical damage to RNA has been hypothesized to lead to the production of toxic protein products. Even more detrimental is the ability of damaged mRNA to drastically affect ribosome homeostasis through stalling. This in turn would lead to greatly diminished translation capacity of cells. Therefore, the inability of cells to recognize and resolve translational-stalling events is detrimental to proteostasis and could even …

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

Arts & Sciences Electronic 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 …

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

Arts & Sciences Electronic 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. …

Investigating The Differentiation And Functional Maturation Of Stem Cell-Derived Β Cells, Leonardo Velazco-Cruz

Arts & Sciences Electronic Theses and Dissertations

Diabetes mellitus is a chronic and global disease rapidly growing in prevalence. Diabetes can be characterized by the dysfunction or death of the glucose sensing insulin secreting  cell.  cells are located within the islet of Langerhans (islet), a tissue within the pancreas. Human islets are critical for the study and treatment of diabetes. However, they can only be obtained from cadaveric organ donors. These cadaveric islets do not proliferate and can only be maintained in vitro for short periods of time, making their availability rare and fleeting. Stem cell-derived -like cells can be generated in indefinite amounts and …

Mechanisms For Osteoblast And Osteocyte Initiation And Sustainment Of Bone Formation In Young-Adult And Aged Mice, Taylor Lynn Harris

McKelvey School of Engineering Theses & Dissertations

The cellular mechanisms for loading-induced bone formation, from osteocyte mechano-sensation to osteoblast-directed bone formation, are not well understood. Elucidating these mechanisms and identifying any processes that are disrupted in aged mice can aide in the development of new anabolic drugs for treating diseases like osteoporosis. This thesis begins by investigating the genes expressed by osteocytes following loading at an early mechanosensitive (4-hr) timepoint, and later at a bone-forming (day 5) timepoint. We demonstrated increases in Ngf and Wnt1 in osteocyte-enriched intracortical bone by laser capture microdissection and microarray analysis. These results were important in demonstrating the presence of Ngf in …

Analysis Of Structural Variation And Mtdna Copy Number In Finns, Liron Ganel

Arts & Sciences Electronic Theses and Dissertations

Cardiovascular disease (CVD) is a complex disease responsible for more deaths worldwide than any other cause according to the World Health Organization. Genetic association studies for CVD and related risk factors have successfully identified hundreds of loci associated with these complex diseases and traits, although much of their heritability remains unexplained. Structural variants (SVs) - including insertions, deletions, duplications, and inversions - are an understudied class of genomic variation that have the potential to explain much of the missing heritability of CVD and other complex traits. Here, we discuss advances emerging from the study of SVs in the context of …

Understanding Immune Responses With Single-Cell Rna Sequencing And Cytof Across Different Diseases And Model Organisms, Ekaterina Esaulova

Arts & Sciences Electronic Theses and Dissertations

The immune system is an integral part of a healthy functioning organism. Immune responses during the disease are complex and include the interplay of many cell subsets. Integrated genomics and bioinformatics usage can yield unique insights into the immune system’s function in health and disease at a single-cell resolution. Here we utilize complimentary single-cell profiling technologies, scRNA-seq and CyTOF, to explore immune responses across diseases and model organisms. Our approach included leveraging scRNA-seq on few samples to understand the immune response landscape and select key markers for a follow-up protein level validation using an appropriate number of replicates by FACS …

Role Of Secretory Leukocyte Protease Inhibitor In Urinary Tract Infection, Anne Rosen

Arts & Sciences Electronic 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. …