Genetics Commons^™

Quantifying Genetic Diversity In Nematode Feeding Rate, Jacob King

Honors Theses

Understanding how populations persist under changing environmental conditions is a central question in ecology and evolutionary biology. Variation in traits related to resource acquisition may play a key role in determining population survival when resources are limited or fluctuate over time. In this study, I investigated how variation in feeding-related traits influences population persistence using a combination of computational modeling and laboratory experiments. I developed a stochastic, individual-based consumer–resource model to simulate population dynamics across varying levels of trait variance and resource regimes. Across 60,000 simulated populations, increased trait variation consistently reduced extinction risk and extended persistence time, although the …

Using The Flexon Approach To Rnai For Analysis Of Gene Function In Gonadal Development In C. Elegans, Andrew D. Spalding

Undergraduate Theses

C. elegans, a nematode worm, was used as a model organism to analyze the developmental effects of knocking down the expression of genes that are both essential to worm viability and highly enriched in reproductive tissues. In earlier research, approximately 70 C. elegans genes were identified that are both gonad-enriched and essential. To prioritize which genes should be the focus of future studies, a new strain of C. elegans was produced with three specific genetic variations that: 1) silence essential, somatic gonad-enriched gene expression, 2) limit the effects of this gene silencing to the gonad, and 3) yield a …

How To Measure, Analyze, And Interpret Age-Related Changes In Caenorhabditis Elegans: Lessons For Mechanistic And Evolutionary Theories Of Aging, Zuzana Kocsisova, Brian M. Egan, Andrea Scharf, Xavier Anderson, Franziska Pohl, Aaron Anderson, Kerry Kornfeld

Biological Sciences Faculty Research & Creative Works

Aging is characterized by progressive degenerative changes in tissue organization and function, some of which increase the probability of mortality. Major goals of aging research are to elucidate the series of events that cause degenerative changes, and to identify environmental, pharmacological, and genetic factors that influence these changes; this information might lead to new strategies to extend health span and lifespan. Mechanistic studies of aging depend on accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here, we review studies that describe age-related changes in C. elegans, including measurements of integrated functions such as behavior …

Bmp Signaling Co-Regulation Of Immune Response And Lipid Metabolism, Katerina K. Yamamoto

Dissertations, Theses, and Capstone Projects

The Bone Morphogenetic Proteins (BMPs) are secreted peptide ligands of the Transforming Growth Factor beta (TGF-β) family, initially identified for their roles in development and differentiation across animal species. They are now increasingly recognized for their roles in physiology and infectious disease. In the nematode Caenorhabditis elegans, the BMP ligand DBL-1 controls fat metabolism and immune response, in addition to its roles in body size regulation and development. DBL-1 regulates classical aspects of innate immunity, including the induction of anti-microbial peptides. We theorized that BMP-dependent regulation of fat metabolism could also promote resilience against microbial pathogens. We found that …

Rnai Pathway Homeostasis Is Essential For Longevity In C. Elegans., Sejal Dulal

2025 Spring Honors Capstone Projects - Archive

RNA interference (RNAi) is a gene regulatory mechanism that is conserved across all animal species, including humans and the microscopic nematode, Caenorhabditis elegans. Many studies have identified the RNAi pathway factors and dissected the regulatory mechanisms of RNAi pathways, but there is little understanding of how the RNAi pathways themselves are regulated. Previously, Rogers and Phillips identified a feedback loop mediated by a pair of small RNA sensors, Sensor of siRNAs-1 (sosi-1) and eri-6[e-f], embedded within the genomic locus of a small RNA biogenesis factor, ERI-6/7. In this feedback motif, loss of small RNA-mediated silencing of …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Gonadal Absence Of Ceh-22: Degradation Of Ceh-22 In The Gonads Of Caenorhabditis Elegans, Andreya C. White

Undergraduate Theses

The reproductive system of hermaphrodite Caenorhabditis elegans (C. elegans) comprises two gonadal arms, each with a terminating distal tip cell (DTC), connected by a common uterus. The DTC has two functions: leader and niche. In C. elegans, ceh-22/nkx2,5 has been found to work together with Wnt signaling to determine the fates of the DTC (Lam et al., 2006). This is an indication that ceh-22 aids in the specification of DTCs. Our research aims to determine the specific function of ceh-22 in the gonad of both male and hermaphrodite C. elegans. This will be accomplished by observing …

Autophagy And Meiotic Fidelity In C. Elegans, Kaitlin E. Kosinski

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionarily conserved multi-step recycling process in which cellular material is enclosed in the double membrane-bound autophagosome, which fuses with the lysosome to degrade its contents. Autophagy is essential for development and cellular adaptation to environmental or intracellular stress and is an important regulator of germline stem cell homeostasis in the model nematode C. elegans. We sought to determine if autophagy is important for genome stability during meiosis and found that the core adult C. elegans autophagy genes bec-1, atg-7, unc-51, and atg-18 were all required for proper meiotic development of oocytes. Loss of these …

Exploring The Functional Significance Of A Yap1 Missense Variant Of Uncertain Significance In Caenorhabditis Elegans, Nathan Jones

Theses

Polycystic ovary syndrome (PCOS) is a complex disorder with various implications, such as polycystic ovaries, visceral obesity, and increased risk of cancer. YAP1 was recently identified as a gene of interest in the development of PCOS. Researchers have established that single nucleotide variants in YAP1 are likely to play a role in PCOS development. This project aims to provide insight into the potential impact of a YAP1 variant of uncertain significance (VUS). Studies in C. elegans have established yap-1 as a nematode ortholog for human YAP1. A YAP1 VUS was identified through ClinVar, YAP1 c.1015A>G (p.Asn339Asp). Evolutionary conservation …

Rnai “Flexon” Approach To Gonad Gene Knockdown In C. Elegans, Sofia Suzanne Douglas

Undergraduate Theses

All living things require some form of genetic regulation so that gene products are correctly produced and maintained. One significant form of post-transcriptional gene expression is RNA silencing, a biological mechanism in which double stranded RNA molecules inhibit gene expression by blocking translation of targeted mRNA molecules. Due to its extensive applications in biotechnology, it’s been adapted as an experimental technique referred to as RNAi. This technique is temporary, transient, and easy to use. A new form of RNAi, referred to as the “Flexon” technique, is a novel approach that provides a method for post-transcriptional gene regulation that allows for …

Exploring The Potential Pathogenicity Of A Type 2 Diabetes Mellitus Associated Insr Missense Variant Of Uncertain Significance Through Daf-2 In The Caenorhabditis Elegans Model, Brittany White

Theses

Type 2 diabetes mellitus (T2DM) is hallmarked by insulin resistance, with the INSR gene identified as a key player in this condition in humans. This gene is known to harbor genetic variants with a wide range of clinical significance from pathogenic to variants of uncertain significance (VUS) to benign. This project investigates a VUS associated with T2DM identified through ClinVar. A gene mutational analysis, predictive amino acid substitution analysis, and protein modeling predict INSR c.1628C>T (p. Thr543Met) to be likely pathogenic or damaging. PolyPhen-2 predicts this variant to be probably damaging (HumDiv score of 1.000).

Evolutionary conservation of the …

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 …

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 …

Reverse Genetics: Downregulating Chk-1 And Fasn-1 In The Gonads Of C. Elegans, Sam Thompson

Undergraduate Theses

Despite its widespread use in research, the model organism C. elegans has several biological processes like gonadal development with potentially unexplored genetic regulators. Previous transcriptome analysis has identified several genes that are upregulated in a specific tissue or sex during the development of the somatic gonad in C. elegans (Kroetz et al. 2015) that have not been previously connected to this process. Of these genes, this research is concerned with chk-1 and fasn-1. Abrogating the expression of these genes in gonadal tissue during gonadogenesis could cause a change in phenotype for affected C. elegans that would aid in understanding these …

Gonads Without Glp-1: Silencing Glp-1 In The Male Somatic Gonad In Caenorhabditis Elegans, Matthew Titus

Undergraduate Theses

In C. elegans, the gene glp-1 encodes for a Notch receptor called GLP-1, one of two found in C. elegans’ genome. The gene has been previously implicated in the development of the hermaphroditic germline as well as playing a role in the mitosis/meiosis decision. Genetic screening has further identified it as potentially playing a role in the development of the male somatic gonad, making it an ideal candidate for a reverse genetic. We did this by silencing glp-1 and observing if any alterations to the gonad’s phenotype occur.

Normally this could be done by performing a gene knockout. …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

Elucidating The Role Of Apl-1, The C. Elegans Ortholog Of The Human Amyloid Precursor Protein, Adanna G. Alexander

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, impacting approximately 6 million Americans. AD is the leading cause of dementia amongst the aged population. Post mortem analysis of the brains of AD patients shows high quantities of extracellular Aβ peptide deposits, which are derived from cleavage of the amyloid precursor protein (APP). Mutations in APP and proteins responsible for APP cleavage, PSENs, greatly increase the incidence of developing AD at an early age. Despite its strong correlation to the progression of AD, the role of APP remains unclear.

Here we investigate the role of the Caenorhabditis elegans ortholog, APL-1. We …

Phenotypic Characterization Of Pnpase Mutation And Overexpression In C. Elegans, Brian J. Hur

Theses and Dissertations

PNPase, polynucleotide phosphorylase, is a multifunctional exoribonuclease protein with 3` terminal oligonucleotide polymerase activity. Coded by the PNPT1 gene, the protein is associated with mitochondrial homeostasis and functions as a possible target for cancer therapy. In this study, C. elegans was used to investigate the effect of mutation and overexpression of pnpt-1, the gene that encodes PNPase. It was determined that two specific mutations in pnpt-1 did not affect PNPase expression nor did they produce deleterious phenotypes that affected polycistronic transcript accumulation or ROS production. Creation of a stable overexpression model was achieved through Fusion PCR. However, different transgenic …

Integration Of Bmp And Insulin/Igf-1 Signaling Regulates Multiple Homeostatic Functions In Caenorhabditis Elegans, James F. Clark

Dissertations, Theses, and Capstone Projects

The maintenance of homeostatic functions is key to the survival and well-being of an organism. Regulation of homeostasis relies on varied inputs, both intrinsic and extrinsic, to potentiate a web of interconnected signaling relays. Insulin/IGF-1 signaling (IIS) is a well-known regulator of glucose and lipid metabolism, as well as having far reaching effects in other homeostatic mechanisms. On the other hand, bone morphogenetic protein (BMP), a member of the transforming growth factor beta signaling superfamily, is known for its role in differentiation and development, with only recent studies highlighting potential roles in metabolic homeostasis. Here we elucidate new functions for …

Loss Of Function Of Gene X Protects Against Α-Dicarbonyl Stress Through The Skn-1 Pathway In C. Elegans, Austin Lim

Dissertations, Masters Theses, Capstones, and Culminating Projects

Diabetes mellitus and Parkinson’s Disease (PD) are debilitating diseases that are increasing in prevalence worldwide. One potential cause of these diseases is the accumulation of advanced glycation end products (AGEs), which are macromolecules that cause irreversible damages. AGEs are a diverse group of highly oxidative byproducts produced from α-dicarbonyl compounds (α-dcs), which are highly reactive molecules that bind indiscriminately to protein and DNA and, are regulated by a conserved glyoxalase system (GLO1 and DJ-1) in humans. Utilizing the conserved glyoxalase system, we were able to establish within a C. elegans model that when this glyoxalase system is impaired, …

Glutamylation Regulates Transport, Specializes Function, And Sculpts The Structure Of Cilia, Robert O'Hagan, Malan Silva, Ken Cq Nguyen, Winnie Zhang, Sebastian Bellotti, Yasmin Ramadan, David Hall, Maureen M. Barr

Department of Biology Faculty Scholarship and Creative Works

Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a “Tubulin Code” that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of kinesin-2 OSM-3/KIF17, while a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here, we examine the role of PTMs and the Tubulin Code in the cililary …

Functional Analysis Of Microrna Pathway Genes In The Somatic Gonad And Germ Cells During Ovulation In C. Elegans, Carmela Rios

Dissertations (1934 -)

MicroRNAs (miRNAs) are post-­transcriptional regulators of gene expression that play critical roles in animal development and physiology, though functions for most miRNAs remain unknown. Worms with reduced miRNA biogenesis due to loss of Drosha or Pasha/DGCR8 activity are sterile and fail to ovulate, indicating that miRNAs are required for the process of oocyte maturation and ovulation. Starting with this penetrant sterile phenotype and using new strains created to perform tissue-­specific RNAi, we characterize the roles of the C. elegans Pasha, pash-­1, and two miRNA-­specific Argonautes, alg-­1 and alg-­2, in somatic gonad cells and in germ cells in the regulation of …

Pnpase In C. Elegans: Mutagenic Analysis To Complement Knockdown Studies, Danielle K. Seibert

Theses and Dissertations

PNPase is a gene implicated as a potential target for cancer therapy; human mutations also present with deafness, myopathies, and neuropathies. In this study, C. elegans was used to investigate the effect of knocking out PNPase in a whole animal. C. elegans knockdown studies have reported an extended lifespan via an increase in ROS production. Further noted are larger mitochondria and an increase in fzo-1 expression. Knockout animals previously constructed using CRISPR/Cas9 were used for this study. We aimed to confirm these findings validating previous studies. It was discovered that PNPase knockout animals demonstrated a similar lifespan extension that was …

Transgenerational Epigenetic Inheritance Via Environmental Stress In Caenorhabditis Elegans, Monica A. Arroliga

Dissertations, Masters Theses, Capstones, and Culminating Projects

No abstract available

Role Of Bec-1/Beclin 1 And Autophagy Genes In C.Elegans Germline Cell Proliferation, Kristina Ames

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionary conserved process involved in the cellular adaptation to stress and basal levels of autophagy are crucial for cellular metabolism and homeostasis. Cellular recycling by autophagy is characterized by the formation of distinctive double-membrane vesicles (autophagosomes) that engulf unnecessary cytoplasmic components, such as organelles and long-lived proteins. Failure to remove protein aggregates and/or damaged organelles, via autophagy, has been implicated in various medical conditions such as liver disease, neurodegenerative diseases and cancer. Autophagy may suppress or promote cellular proliferation in tumors, depending on the type and metabolic state of the cell, where autophagy is generally believed to …

Reactive Oxygen Species-Mediated Neurodegeneration Is Independent Of The Ryanodine Receptor In Caenorhabditis Elegans, Lyndsay E.A. Young, Daniel C. Williams

Journal of the South Carolina Academy of Science

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca²⁺) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the …

Phenotypic Characterization Of Pnpase Knockdown In C. Elegans, Laura A. Lambert

Theses and Dissertations

The multifunctional exoribonuclease protein PNPase is implicated as a potential target for cancer therapy as well as causing mitochondrial disorders in humans, but there has yet to be a whole animal knockdown model created. In this study, C. elegans was used to investigate the effect of knocking down pnpt-1, the gene that encodes PNPase. It was discovered that pnpt-1 knockdown significantly extends lifespan via an increase in superoxide production similar to other known mitochondrial lifespan extension pathways. Additionally, mitochondrial networks, size and respiration are affected indication of other mitochondrial dysfunction..

PNPase is also known to transport small RNAs into the …

Profile Of The Unfolded Protein Response In C. Elegans Depleted Of The Translational Chaperone, Nac., Caylin S. Murray

Masters Theses, 2010-2019

The function of a protein is a direct consequence of its final structure, which is achieved by protein-folding processes that generate a tertiary state through the juxtaposition of locally formed secondary structures. Because all cells need functional proteins to survive, each contains robust and redundant mechanisms that regulate the folding of newly forming proteins, and the refolding of misfolded proteins that are often generated during stress. Essential to these mechanisms, chaperones are proteins that aid in protein folding of nascent and misfolding protein without being incorporated in the final structure. One chaperone complex, the nascent polypeptide-associated complex (NAC), aids in …

Sirt1 Regulation Of The Heat Shock Response In An Hsf1-Dependent Manner And The Impact Of Caloric Restriction, Rachel Rene Raynes

USF Tampa Graduate Theses and Dissertations

The heat shock response (HSR) is the cell's molecular reaction to protein damaging stress and is critical in the management of denatured proteins. Activation of HSF1, the master transcriptional regulator of the HSR, results in the induction of molecular chaperones called heat shock proteins (HSPs). Transcription of hsp genes is promoted by the hyperphosphorylation of HSF1, while the attenuation of the HSR is regulated by a dual mechanism involving negative feedback inhibition from HSPs and acetylation at a critical lysine residue within the DNA binding domain of HSF1, which results in a loss of affinity for DNA. SIRT1 is a …

Asymmetric Localizations Of Lin-17/Fz And Mig-5/Dsh Are Involved In The Asymmetric B Cell Division In C. Elegans, Mingfu Wu, Michael A. Herman

School of Biological Sciences: Faculty Publications

LIN-44/Wnt and LIN-17/Frizzled (Fz) function in a planar cell polarity (PCP)-like pathway to regulate the asymmetric B cell division in Caenorhabditis elegans. We observed asymmetric localization of LIN-17/Frizzled (Fz) and MIG-5/Disheveled (Dsh) during the B cell division. LIN-17∷GFP was asymmetrically localized within the B cell prior to and after the B cell division and correlated with B cell polarity. Asymmetric localization of LIN-17∷GFP was dependent upon LIN-44/Wnt and MIG-5/Dsh function. The LIN-17 transmembrane domain and a portion of the cysteine-rich domain (CRD) were required for LIN-17 function and asymmetric distribution to the B cell daughters, while the conserved KTXXXW …