Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Transcription And Translation Regulation Of Germ Cell To Maternal Transition, Noor Kotb

Electronic Theses & Dissertations (2024 - present)

In sexually reproducing organisms, the process of gametogenesis produces mature eggs and sperms required for fertilization to occur. The egg's quality is crucial for the healthy development of the next generation, making oogenesis a tightly regulated process with multiple benchmarks. To investigate the intricacies of oogenesis, we utilized the Drosophila oogenesis system as our primary model. This choice was motivated by several factors. Firstly, the process of egg development in Drosophila is conserved across species, making it a valuable proxy for understanding oogenesis in other organisms, including humans. Secondly, Drosophila melanogaster has long been established as a powerhouse in genetic …

Robust Phylogenetic Regression, Richard Adams, Zoe Cain, Raquel Assis, Michael Degiorgio

Entomology and Plant Pathology Faculty Publications and Presentations

Modern comparative biology owes much to phylogenetic regression. At its conception, this technique sparked a revolution that armed biologists with phylogenetic comparative methods (PCMs) for disentangling evolutionary correlations from those arising from hierarchical phylogenetic relationships. Over the past few decades, the phylogenetic regression framework has become a paradigm of modern comparative biology that has been widely embraced as a remedy for shared ancestry. However, recent evidence has shown doubt over the efficacy of phylogenetic regression, and PCMs more generally, with the suggestion that many of these methods fail to provide an adequate defense against unreplicated evolution—the primary justification for using …

Investigating The Function Of Protein S-Acyltransferase 2 In Arabidopsis Thaliana Using Crispr Mutants, Nicole Benjamin

Honors Theses and Capstones

Arabidopsis thaliana contains 24 Protein Acyl Transferases (PATs). These enzymes are responsible for catalyzing the addition of a palmitate to a target substrate (palmitoylation). However, beyond its broad enzymatic function, it is unknown how PATs interact on a cellular level. This research focuses on identifying the function of PAT2. CRISPR-Cas9 was used to create deletion mutations that would result in a non-functional PAT. Two plants homozygous for a pat2 deletion were identified: pat2-5 and pat2-6. Preliminary results suggest that pollen grains in both pat2 mutants are larger in both length and width. Additionally, it appears that mutant pollen tends to …

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …

Can Edna Be Used To Locate Shawnee Hills Cavefish Forbesichthys Papilliferus?, Megan Brandt, Timothy Spier Phd, Gary Zeruth Phd

Murray State Theses and Dissertations

Traditional stream fish sampling methods, such as seining and electrofishing, are time consuming, expensive, and limited to short stretches of stream. However, the analysis of environmental DNA (eDNA) from water samples promises to be a quick, inexpensive method for detecting fish. The streams of the Land Between the Lakes Recreational Area (LBL) are unique, undisturbed streams which contain many interesting fish species for which little information exists. One such rare species is the Shawnee Hills Cavefish Forbesichthys papilliferus, which is known to exist in a few LBL streams. However, the complete distribution of the Shawnee Hills Cavefish in LBL …

The Effects Of Early Exposure To Prescription/Illicit Drugs And Drug Metabolites On Larval Zebrafish Behavioral And Motor Function Development, Jacob Thomas, Dena Weinberger, Bikram Subedi, Brandon Capps

Murray State Theses and Dissertations

THE EFFECTS OF EARLY EXPOSURE TO PRESCRIPTION/ILLICIT DRUGS AND DRUG METABOLITES ON LARVAL ZEBRAFISH BEHAVIORAL AND MOTOR FUNCTION DEVELOPMENT

A Thesis Presented to the Faculty of the Department of Biology

Murray State University

Murray, Kentucky

In Partial Fulfillment of the Requirements for the Degree of Masters In Science

By Jacob Thomas, B.S., Murray State University

December 2024

Acknowledgements

Brandon Capps, who pretty much did a whole third of the legwork on this project and saved me lots of headaches;

Chandler Maddox, one of the University of Kentucky’s finest undergrads who came in from the top rope with a folding chair …

Evaluating The Utility Of Tracers To Characterize Environmental Dna Transport And Inform Detection Of Fishes In Small Streams, Gavin B. Bandy

Cal Poly Humboldt theses and projects

This study was motivated by the need to develop a noninvasive and highly sensitive monitoring tool for determining local occupancy of an endangered aquatic species To make inference into the occupancy of fishes within small stream sites, we developed a method to determine whether environmental DNA (eDNA) concentrations from a target species were elevated relative to a tracer, formulated to mimic eDNA and introduced at a single location. We examined patterns in the observed distribution of the tracer to account for the effects of site-specific transport processes and sampling on distributions of naturally occurring eDNA at small spatial scales (400 …

Csn-5: A Tumor's Friend Or Foe In The C. Elegans Germline?, Kellie C. Kuch

Graduate Student Theses, Dissertations, & Professional Papers

The COP9 signalosome is a highly conserved eukaryotic complex regulating protein degradation via deneddylation of Cullin-RING E3 ligases. CSN5, the COP9’s fifth component, contains the catalytically active domain for CSN deneddylation. The complex is inactive without CSN5; however, CSN5 engages in COP9-independent binding with several other proteins, typically promoting either destruction or stabilization of its partners. Many of its confirmed interaction partners are also implicated in tumorigenesis (prominent examples being p27 and p53) and a complex cancer interactome has been established for CSN5. Additionally, CSN5 overexpression has been documented in a staggering array of cancers of diverse origins. This discovery …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

A Multimolecular Perspective On The Success Of Wolf Recovery And Relocation, Samuel D. Hervey

Dissertations, Master's Theses and Master's Reports

With global biodiversity in decline and many species isolated in fragmented habitats, conservation efforts increasingly rely on natural recolonization and translocation to restore ecosystems. These strategies face challenges such as genetic erosion and habitat limitations, highlighting the need for effective monitoring practices. This research assesses the success of wolf recovery initiatives by examining long-term genetic and genomic health using both traditional and advanced molecular methods. First, we investigated the genetic health of 19 gray wolves (Canis lupus) relocated to Isle Royale National Park to restore ecosystem balance. Initial genetic assessments with microsatellites found that these wolves had genetic diversity metrics …

ฤทธิ์ของสารสกัดจากมะกรูดต่อภาวะเครียด Oxidative Stress ในหนอน Caenorhabditis Elegans, ณัฐพงศ์ นพโลหะ

Chulalongkorn University Theses and Dissertations (Chula ETD)

ภาวะโรคไม่ติดต่อเรื้อรัง หรือ Non-Communicable Disease (NCDs) เป็นภาวะโรคที่ไม่ได้ติดต่อจากคนสู่คนได้รวมถึงไม่ได้เกิดจากการติดเชื้อโรค โดยสาเหตุหนึ่งของภาวะกลุ่มโรคนี้คือการเกิดภาวะ oxidative stress ที่ทำให้ร่างกายมีปริมาณของสารอนุมูลอิสระไม่สมดุล โดยที่ผ่านมาจำนวนผู้ป่วยในโรคนี้มีจำนวนเพิ่มขึ้นอย่างต่อเนื่อง ซึ่งแนวทางการรักษาส่วนใหญ่มักจะมาจากการรักษาตามอาการ ดังนั้นการแก้ปัญหาโรคนี้ให้ได้ผลมากที่สุดคือการป้องกันการเกิดโรคมากกว่าการรักษา ผู้วิจัยจึงสนใจที่จะนำมะกรูดที่มีสรรพคุณต้านอนุมูลอิสระมาทดสอบ โดยมีวัตถุประสงค์เพื่อศึกษาฤทธิ์ของสารสกัดจากใบมะกรูดและผิวมะกรูด ในการช่วยลดการเกิดภาวะ oxidative stress สำหรับการช่วยยืดอายุของ C. elegans ที่ถูกชักนำให้เกิดภาวะ oxidative stress โดยแบ่งการศึกษาออกเป็น 4 ขั้นตอน ได้แก่ ตอนที่ 1 ศึกษาฤทธิ์ของสารสกัดจากมะกรูดต่อ E.coli OP50 ที่เป็นอาหารของ C. elegans พบว่าสารสกัดจากใบมะกรูดและผิวมะกรูดไม่มีผลในการยับยั้งการเจริญของ E.coli OP50 เมื่อเทียบกับการยับยั้งการเจริญเติบโตของยา Penicillin-Streptomycin ที่ใช้เป็นกลุ่มควบคุม จึงสามารถใช้สารสกัดจากใบมะกรูดและผิวมะกรูดในการทดสอบได้ โดยที่ไม่มีผลต่อ E.coli OP50 ที่ใช้เป็นอาหารของ C. elegans ตอนที่ 2 การศึกษาฤทธิ์ของสารสกัดจากใบมะกรูดและผิวมะกรูดที่มีผลต่อการรอดชีวิตของ C. elegans ที่ถูกชักนำให้เกิดภาวะ oxidative stress พบว่าสารสกัดจากใบมะกรูดและผิวมะกรูดที่ความเข้มข้น 50 , 100 และ 200 ug/ml มีอัตราการรอดชีวิตของ C. elegans เมื่อเทียบกับ C. elegans ที่ไม่ได้ให้สารสกัดจากใบมะกรูดและผิวมะกรูด แตกต่างกันอย่างมีนัยสำคัญทางสถิติ 0.05 และตอนที่ 3 การศึกษาฤทธิ์ของสารสกัดจากใบมะกรูดและผิวมะกรูดต่อการยับยั้งปริมาณ ROS ของ C. elegans ที่ถูกชักนำให้เกิดภาวะ oxidative stress โดยพบว่าใบมะกรูดและผิวมะกรูดที่ความเข้มข้น 50 , 100 และ 200 ug/ml มีค่าปริมาณสาร ROS ของ C. elegans ที่ให้สารสกัดจากใบมะกรูดและผิวมะกรูด เมื่อเทียบกับ C. elegans ที่ไม่ให้สารสกัดจากใบมะกรูดและผิวมะกรูด …

การปรับสมดุลไมโครไบโอมในลำไส้ด้วยเชื้อ Lactobacillus Rhamnosus Gg ช่วยบรรเทาความรุนแรงจากการติดเชื้อในกระแสเลือด ในหนูที่ถูกเหนี่ยวนำให้เกิดความชราโดยน้ำตาล D-Galactose และกระตุ้นภาวะติดเชื้อในกระแสเลือดโดยวิธีการผูกและเจาะลำไส้ใหญ่ส่วนต้น, ชาลิสา พินิจจันทร์

Chulalongkorn University Theses and Dissertations (Chula ETD)

การเสียสมดุลของจุลินทรีย์ในลำไส้อาจทำให้เกิดภาวะลำไส้รั่ว เกิดการติดเชื้อในกระแสเลือดตามมาได้ ซึ่งสภาวะดังกล่าวมักพบมากในผู้สูงอายุ การศึกษาก่อนหน้านี้พบว่าโพรไบโอติกสามารถลดการเสียสมดุลของจุลินทรีย์ในลำไส้ แต่การศึกษาเรื่องผลของการรับประทานเชื้อโพรไบโอติดต่อของการลดความรุนแรงจากการติดเชื้อในกระแสเลือด รวมทั้งภาวะ Sepsis-associated encephalopathy (SAE) ในผู้สูงอายุนั้นยังไม่มีการศึกษาที่ชัดเจน วัตถุประสงค์ของการศึกษา เพื่อทดสอบความสามารถของเชื้อโพรไบโอติกสายพันธุ์ Lacticaseibacillus rhamnosus GG (LGG) ในการช่วยลดความรุนแรงของการติดเชื้อในกระแสเลือดในหนูที่ถูกเหนี่ยวนำให้เกิดสภาวะชราโดยการใช้น้ำตาลกาแลคโตส ผู้วิจัยทำการให้เชื้อ LGG ทางปากกับหนูทดลอง เปรียบเทียบกับกลุ่มควบคุม และทดสอบความแตกต่างของจุลินทรีย์ในลำไส้ในอุจจาระของหนูด้วยวิธี 16S RNA sequencing พร้อมวัดสภาวะความชราของหนูด้วยเทคนิค Histochemistry ในอวัยวะภายใน จากนั้นหนูทั้ง 2 กลุ่มจะถูกกระตุ้นให้เกิดการติดเชื้อในกระแสเลือดโดยวิธีการผูกและเจาะลำไส้ใหญ่ส่วนต้น (CLP) และวัดความรุนแรงของการติดเชื้อในกระแสเลือดโดยการวัดอัตราการตาย ระดับ creatinine (Scr), Alanine transaminase (ALT), cytokines (IL-6 TNF-α IL-10 และ IL-1ß) ในซีรัมโดยเทคนิค Enzyme-linked immunosorbent assay (ELISA) การตรวจวัด Sepsis encephalopathy ผู้วิจัยใช้ค่ามาตรฐาน SHIRPA เพื่อช่วยในการวัด นอกจากนี้เพื่อหาสาเหตุของการลดความรุนแรงจากการติดเชื้อในกระแสเลือดด้วยเชื้อโพรไบโอติก ผู้วิจัยนำ Lactobacillus condition media (LCM) ร่วมกับ Lipopolysaccharide (LPS) มาใช้ในการกระตุ้นเซลล์ RAW 264.7 , เซลล์ BV-2 และเซลล์ HT-22 จากนั้นทำการวัดปริมาณ Inflammatory cytokines ด้วยเทคนิค ELISA และวัดการแสดงออกของยีน IL-6 TNF-α IL-10 IL-1ß Fizz Arg-1 NF-kB TLR-4 และยีน iNOS ด้วยเทคนิค Quantitative real-time PCR (qPCR) จากผลการวิเคราะห์จุลินทรีย์ในอุจจาระ แสดงให้เห็นว่าหนูชรามีการสูญเสียสมดุลของจุลินทรีย์ในลำไส้ และพบการเกิดพังผืดในปอด ไต และตับ ซึ่งเชื้อ …

Do Duckweeds Adapt To Water And Microbes?, Ava M. Rose

Honors Theses and Capstones

Organisms in their home environment sometimes outperform transplanted individuals native to other areas, in a phenomenon termed local adaptation. While local adaptation is traditionally considered to be driven by the abiotic factors of an environment, scientists have recently increased consideration of biotic factors. Specifically, of interest to many is host-associated microbiomes, which can alter host trait expression. As the desire to commercialize microbiome treatments for agriculture and medicine grows, it is important to analyze the potential value of local microbiomes, which may be adapted to their hosts, or to which local hosts may have adapted. Using Lemna minor (duckweed) as …

Consequences Of Spatial Structure In Soil–Geomorphic Data On The Results Of Machine Learning Models, Daehyun Kim, Insang Song, Lorrayne Miralha, Daniel R. Hirmas, Ryan W. Mcewan, Tom G. Mueller, Pavel Samonil

Biology Faculty Publications

In this paper, we examined the degree to which inherent spatial structure in soil properties influences the outcomes of machine learning (ML) approaches to predicting soil spatial variability. We compared the performances of four ML algorithms (support vector machine, artificial neural network, random forest, and random forest for spatial data) against two non-ML algorithms (ordinary least squares regression and spatial filtering regression). None of the ML algorithms produced residuals that had lower mean values or were less autocorrelated over space compared with the non-ML approaches. We recommend the use of random forest when a soil variable of interest is weakly …

The Effect Of Db1976 On The Fibrotic Response In Three-Spined Stickleback (Gasterosteus Aculeatus), Saif Quraishi

Honors Scholar Theses

The study of fibrosis in stickleback has been a growing field in which there have been a few studies conducted. This study examines two experiments involving the inhibition of fibrosis in stickleback. The first experiment used fish from the Kenai River Flats (KRF) in Alaska. The second experiment used fish from Roselle Lake in British Columbia, Canada. To determine the impact the drug had on fibrosis, sticklebacks from the KRF population were treated with DB1976 as well as alum, a pro‐inflammatory vaccine adjuvant that causes fibrosis (Kool et. al 2012). When each DB1976 + alum treatment group was compared with …

A Timeline Of Klinefelter’S Syndrome, Xxy, Emma Chevalier, Tyler Venegas, Mary Salibi

Undergraduate Research Symposium Posters

Klinefelter Syndrome (KS) is a non-mendelian chromosomal disorder consisting of supernumerary X chromosomes in males, 80% of which manifest as the 47,XXY karyotype. The resulting gene dosage abnormalities affect both cognitive and physical development, with variable expressivity. The disease was first described by Harry Klinefelter in 1942 and was thought to be an endocrine disorder until the late 1950s, when karyotyping of affected individuals revealed an extra X chromosome.

(It is the most common sex chromosome aneuploidy (1:500 males) and the most common cause of azoospermia. The phenotype for KS is highly contested due to its extremely variable expressivity and …

A Genetic Screen For Metabolic Modulators In Drosophila Melanogaster, Victoria Campos, Logan Kazimer, Brandon Polimeni, Katelyn Niswonger, Matthew Meiselman

Undergraduate Research Symposium Posters

When environments become unfavorable, to preserve energy, animals will attenuate reproduction and limit growth. This evolutionary strategy requires perceiving and assessing a complex environment, a long-standing role of the nervous system. However, the nervous system’s control over endocrine states remains a monumental challenge. Here, we propose to exploit the genetic accessibility and cellular resolution readily found in Drosophila melanogaster, to fully explore how the brain controls metabolic and reproductive states. This project relies on the Meiselman Lab’s established unbiased neural activation screen, which located new neural circuits that participate in metabolic control. The project proposes the use of the split …

Increased Coding Potential Of Bovine Herpesvirus 1, Victoria Jefferson

Theses and Dissertations

Bovine respiratory disease (BRD) costs the cattle industry millions of dollars in costs in treatment and loss every year in the United States. A significant pathogen often contributes to BRD is Bovine Herpesvirus 1 (BoHV-1), a double stranded DNA virus with the ability to establish latency in the trigeminal ganglia and neurons. Primary infection with BoHV-1 results in immunosuppression that increases the risk of secondary bacterial infection and pneumonia. Because herpesviruses infect their hosts for life and can be reactivated in times of stress, BoHV-1 can present a recurring risk of BRD. The following research aims to expand the knowledge …

Towards Understanding The Interactions Between Ospreys And Human-Made Structures In The Tennessee River Valley, Natasha Karina Murphy

Theses and Dissertations

Raptor nests on human-built structures represent a significant source of conflict as they can result in bird mortality, fires, structure damage, service distribution, or power outages when falling nest materials or animals connect with energized conductors. Power companies, such as the Tennessee Valley Authority (TVA), wish to mitigate these conflicts to avoid service disruptions. In this dissertation, I present my work towards understanding and mitigating the interactions between Ospreys (Pandion haliaetus) and human-made structures. To achieve this, I explored multiple elements of conflict identification, monitoring, and basic ecology of the target species to better inform conflict mitigation. In Chapter I, …

Protective Responses Of The Intestinal Epithelial Cell Line Ht-29 Cells Exposed To Dephosphorylated Salmonella Flagellin [Research Note], Heyeon Baik, Jaiesoon Cho

The Philippine Agricultural Scientist

This study aimed to describe the effects of Salmonella Typhimurium flagellin (SFL) dephosphorylated by sweet potato purple acid phosphatase (PAP) on the protective responses of the intestinal epithelial cell line HT-29 cells. The enzyme was reported to display a broad substrate specificity for various organic phosphorylated conjugates and phosphoproteins. Dephosphorylation of SFL by sweet potato PAP decreased to 35% in the presence of 0.05 mM vanadate as compared with the negative control (p < 0.05). Intact SFL and the SFL treated with sweet potato PAP did not remarkably induce the activation of caspase-3 in HT-29 cells at all the tested levels of the substrate. Intact SFL maximally induced the release of IL (interleukin)-8 in HT-29 cells at 1000 ng/mL (p < 0.05). However, the SFL treated with the enzyme inhibited the release of IL-8 at over 100 ng/mL of the substrate as compared with intact SFL, resulting in an approximately 8-fold decrease even at 1000 ng/mL (p < 0.05). The SFL treated with the enzyme decreased the activation of the total ERK1/2 in the cells to 1.9 and 1.7–fold at 10 and 1000 ng/mL of the substrate, respectively, as compared with intact SFL (p < 0.05). In conclusion, sweet potato PAP could be a promising tool for controlling excessive inflammation during Salmonella infection in animal husbandry, and the enzyme could be a safe alternative that can overcome the drawbacks of chemotherapy.

On The Origin And Evolution Of The Mosquito Male-Determining Factor Nix, James K. Biedler, Azedah Aryan, Yumin Qi, Aihua Wang, Ellen O. Martinson, Daniel A. Hartman, Fan Yang, Atashi Sharma, Katherine S. Morton, Mark Potters, Chujia Chen, Stephen L. Dobson, Gregory D. Ebel, Rebekah C. Kadling, Sally Paulson, Rui-De Xue, Michael R. Strand, Zhijian Tu

Entomology Faculty Publications

The mosquito family Culicidae is divided into 2 subfamilies named the Culicinae and Anophelinae. Nix, the dominant male-determining factor, has only been found in the culicines Aedes aegypti and Aedes albopictus, 2 important arboviral vectors that belong to the subgenus Stegomyia. Here we performed sex-specific whole-genome sequencing and RNAseq of divergent mosquito species and explored additional male-inclusive datasets to investigate the distribution of Nix. Except for the Culex genus, Nix homologs were found in all species surveyed from the Culicinae subfamily, including 12 additional species from 3 highly divergent tribes comprising 4 genera, suggesting Nix originated at least 133 to …

Design And Characterization Of A Novel Eef2k Degrader With Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer, Changxin Zhong, Rongfeng Zhu, Ting Jiang, Sheng Tian, Xiaobao Zhao, Xiaoya Wan, Shilong Jiang, Zonglin Chen, Rong Gong, Linhao He, Jin-Ming Yang, Na Ye, Yan Cheng

Markey Cancer Center Faculty Publications

Dysregulated eEF2K expression is implicated in the pathogenesis of many human cancers, including triple-negative breast cancer (TNBC), making it a plausible therapeutic target. However, specific eEF2K inhibitors with potent anti-cancer activity have not been available so far. Targeted protein degradation has emerged as a new strategy for drug discovery. In this study, a novel small molecule chemical is designed and synthesized, named as compound C1, which shows potent activity in degrading eEF2K. C1 selectively binds to F8, L10, R144, C146, E229, and Y236 of the eEF2K protein and promotes its proteasomal degradation by increasing the interaction between eEF2K and the …

A Study Of The Snd1/Prmt5 Axis In Liver Cancer By Genetic Mouse Models, Tanner Wright, Tanner Wright

Dissertations and Theses (Open Access)

Arginine methylation is an essential post-translational modification (PTM) in cells. Protein arginine methyltransferase 5 (PRMT5) is the primary enzyme that catalyzes symmetric dimethyl arginine (SDMA) and requires methylosome protein 50 (MEP50) for stability and enzymatic activity which are necessary for life and development. Effector proteins bind different types of PTM’s to facilitate signaling. Staphylococcal nuclease Tudor domain containing 1 (SND1) is an effector that specifically binds SDMA via its single C-terminal Tudor domain. Both SND1 and PRMT5 have been implicated in hepatocellular carcinoma (HCC). SND1 has been confirmed as a driver of HCC using genetically engineered mouse models (GEMMs), though, …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Effect Of Plant Genotype On Plant-Microbe Interactions And Multi-Generation Ecosystem Selection Of Microbial Communities Associated With Plant Biomass In Arabidopsis Thaliana, Nachiket Shankar

Graduate Doctoral Dissertations

The microbiome's role in shaping host phenotypes is a critical area of investigation, with implications for ecology, evolution, and host health. Dynamic plant-microbe interactions are influenced by factors like soil type, environment, and genotype. Understanding their impact on microbial communities is key for tailored plant benefits. An artificial ecosystem selection experiment was done for eight generations with Arabidopsis thaliana Ler and Cvi. This revealed distinct microbial communities shaped by genotypes and biomass treatments. Initially, environment dominated, but over time, genotype and biomass gained influence, explaining ~40% of the variation. Moreover, genotype-specific rhizobacterial associations were observed, enhancing understanding of community dynamics …

Characterization Of Developmental Phenotypes In Zebrafish With Mutations In Mmachc, Briana Elise Pinales

Open Access Theses & Dissertations

Methylmalonic aciduria and homocystinuria, CblC type (cblC) syndrome (MIM 277400) is a genetic disorder resulting from a mutation in the MMACHC gene. This gene plays a crucial role as a chaperone in the conversion of vitamin B12 into its active form, which is essential for proper cellular metabolism. cblC syndrome is heterogenous by nature, primarily attributed to the extensive damage it causes across multiple bodily systems. In cases of early onset of cblC syndrome, patients may exhibit a diverse range of clinical symptoms including difficulties with feeding, dysmorphic features, microcephaly, brain abnormalities, hypotonia, developmental delays, and seizures. The study of …

The Application Of Simultaneous Mainstem Bronchus Dilation With Pulmonary Artery Stenting In The Context Of Hypoplastic Left Heart Syndrome, Sylwia Hasterok, Thomas G Scott, Devin G Roller, Adam Spencer, Arun B Dutta, Kizhakke M Sathyan, Daniel E Frigo, Michael J Guertin, Daniel Gioeli

Faculty, Staff and Student Publications

The clinical success of combined androgen deprivation therapy (ADT) and radiotherapy (RT) in prostate cancer created interest in understanding the mechanistic links between androgen receptor (AR) signaling and the DNA damage response (DDR). Convergent data have led to a model where AR both regulates, and is regulated by, the DDR. Integral to this model is that the AR regulates the transcription of DDR genes both at a steady state and in response to ionizing radiation (IR). In this study, we sought to determine which immediate transcriptional changes are induced by IR in an AR-dependent manner. Using PRO-seq to quantify changes …

Multi-Ancestry Genome-Wide Association Study Of Cannabis Use Disorder Yields Insight Into Disease Biology And Public Health Implications, Daniel F Levey, Marco Galimberti, Joseph D Deak, Frank R Wendt, Arjun Bhattacharya, Dora Koller, Kelly M Harrington, Rachel Quaden, Emma C Johnson, Priya Gupta, Mahantesh Biradar, Max Lam, Megan Cooke, Veera M Rajagopal, Stefany L L Empke, Hang Zhou, Yaira Z Nunez, Henry R Kranzler, Howard J Edenberg, Arpana Agrawal, Jordan W Smoller, Todd Lencz, David M Hougaard, Anders D Børglum, Ditte Demontis, Veterans Affairs Million Veteran Program, J Michael Gaziano, Michael J Gandal, Renato Polimanti, Murray B Stein, Joel Gelernter

Faculty, Staff and Student Publications

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within …

Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner

Research, Publications & Creative Work

Genetic analysis in model systems using bioinformatic approaches provides a rich context for a concrete and conceptual understanding of gene structure and function. With the intent to engage students in research and explore disease biology utilizing the nematode Caenorhabditis elegans model, we developed a semester-long course-based undergraduate research experience (CURE) in a hybrid (online/in-person) learning environment—the gene-editing and evolutionary nematode exploration CURE (GENE-CURE). Using a combination of bioinformatic and molecular genetic tools, students performed structure-function analysis of disease-associated variants of uncertain significance (VUS) in human orthologs. With the aid of a series of workshop-style research sessions, students worked in teams …