Genetics and Genomics Commons^™

Architects Of Mrna Fate: Molecular And Cellular Control Of P-Body Organization In The Drosophilia Melanogaster Female Germline, Samantha Milano

Dissertations, Theses, and Capstone Projects

Processing bodies (P-bodies) are cytoplasmic ribonucleoprotein condensates that regulate mRNA storage, translational repression, and decay. While the biochemical principles governing condensate assembly have been extensively studied in vitro, how P-body organization is established and dynamically regulated in vivo to control specific mRNA populations remains poorly understood. This dissertation investigated the molecular and cellular mechanisms that govern P-body architecture and function in the Drosophila melanogaster female germline. First, I identified the conserved LSm protein Trailer Hitch (Tral) as a central organizer of P-body architecture. Using quantitative confocal and super-resolution microscopy combined with chemical perturbations, I showed that Tral coordinates the …

Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel

Dissertations, Theses, and Capstone Projects

Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …

Popgenhelpr: An R Package To Streamline And Facilitate Informed Population Genomic Analyses And Visualization Of Genetic Ancestry, Diversity And Differentiation, Keaka Farleigh, Mason O. Murphy, Christopher Marie Blair, Tereza Jezkova

Publications and Research

Analysing large population genomic datasets requires an interdisciplinary skillset. Beyond a knowledge base in genetics and population biology, population genomic analyses involve computer science and statistics, representing a barrier for researchers without experience in those fields. PopGenHelpR seeks to lower this barrier by enabling researchers to perform population genomic analyses and generate near-publication quality figures in a streamlined and informed fashion. PopGenHelpR allows users to estimate genetic diversity within populations as well as differentiation among populations and individuals from single nucleotide polymorphism data. PopGenHelpR includes commonly used measures such as observed heterozygosity and FST. PopGenHelpR also provides five …

Exploring Biogeographical Ancestry Inference Of New York Residents Using A 45 Indel Panel, Amanda Martinez

Student Theses

Biogeographical ancestry (BGA) inference is an important tool in forensic science, providing supplemental information when comparison/reference DNA is not available for traditional DNA analyses. Insertion/deletion polymorphisms (INDELs) have been used in the last decade as ancestry-informative markers (AIMs) for BGA inference because they can be easily adapted to forensic-type samples and are determined using low cost and easy processing methods. Limited research has attempted to estimate ancestry and admixture in United States (U.S.) populations. This study evaluated the effectiveness of a 45- and 21- INDEL panel to measure population admixture proportions of four different origins (African, European, East Asian and …

Genetic Screen For Regulators Of Pol4, A Dna Repair Polymerase In Saccharomyces Cerevisiae, Pasang Dolma Sherpa

Theses and Dissertations

In Saccharomyces cerevisiae, DNA polymerase 4 (POL4) is the beta repair polymerase, the product of the POL4 gene, and is involved in base excision repair (BER) and microhomology-mediated end joining (MMEJ). Despite its involvement in these repair pathways and its conservation across eukaryotes, deletion of POL4 shows no detectable phenotype under standard laboratory conditions. I hypothesized that unknown genes act as backup systems, providing redundant activities that allow pol4Δ cells to survive. To test this, a genetic screen for mutants showing synthetic lethality with pol4Δ was implemented. I constructed a strain lacking the POL4 gene and carrying …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

Building A Cell Specific System For In Vivo Rna Imaging Of The Endogenous Actin Gene In C. Elegans, Jasmine A. Huerta Canete

Theses and Dissertations

Messenger RNA (mRNA) plays a crucial role in protein synthesis and cellular processes, important for the development of cells such as neurons. When dysregulation occurs, it can lead to outcomes such as aberrant translation, causing neurodegenerative conditions to arise. Unfortunately, the localization of mRNA in an in vivo cell specific manner is still not understood. To address this, we decided to develop a cell-specific system to image RNA in vivo, within the organism known as C. elegans with a focus on the actin gene. The Actin gene encodes for an important cytoskeleton protein expressed ubiquitously, vital for the cell …

Retinal Precursor Cell Enriched Multiomic And Pseudo-Time Analysis Of Developing And Reprogrammed Photoreceptors, Brendon M. Patierno

Dissertations, Theses, and Capstone Projects

The vertebrate retina is a complex tissue made up of seven major cell subtypes which during development must differentiate and localize into a highly organized structure. These neuronal cells do not regenerate if damaged or diseased, and the progressive deterioration of cone photoreceptor cells is the leading cause of age related blindness. Currently there are no cures for this disease, but one promising therapeutic avenue is cell transplantation research. If we can further elucidate the gene regulatory networks that define cone cell development, this knowledge could be applied to the generation of healthy cone cells in clinically relevant models.

The …

Exploring The Role Of Ecological Traits In Shaping Spatial Patterns Of Genetic Diversity, Rilquer Mascarenhas Da Silva

Dissertations, Theses, and Capstone Projects

The field of comparative phylogeography aims at uncovering common underlying causes for shared patterns of diversity and diversification at the population level. However, it is now widely accepted that intraspecific genetic diversity patterns can differ considerably across co-occurring taxa due to ecological processes acting at the population level (and influencing individual movement and abundance). To model the processes underlying lineage diversification and demographic shifts in response to environmental changes, phylogeographers and population geneticists are now faced with the challenge of incorporating measurements of species ecological traits into their molecular studies. This dissertation aimed at investigating how different types of ecological …

Ai-Powered Multi-Omics Integration For Predictive Modeling Of Genotype-Environment-Phenotype Relationships, You Wu

Dissertations, Theses, and Capstone Projects

This dissertation presents a series of machine learning frameworks for modeling genotype–environment–phenotype relationships through integrative predictive modeling of multi-omics data. The work addresses three major axes of biological complexity: modeling biological information transmission cross-levels from genes to proteins to phenotypes, predicting molecular features cross-scale from cells to tissues to organisms, and translating phenotypes cross-species from model systems to humans. Each proposed method also tackles key machine learning (ML) challenges in the biomedical domain, including data scarcity, domain shift, out-of-distribution (OOD) generalization, and hierarchical modeling. Specifically, this dissertation introduces five novel deep learning algorithms: MultiDCP predicts drug-induced transcriptomic and viability responses …

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 …

Origin And Maintenance Of The Andean Bird Fauna, Elkin A. Tenorio

Dissertations, Theses, and Capstone Projects

The origin and maintenance of the tropical montane diversity have been evaluated over multiple decades using various techniques and perspectives. Despite major progress in understanding phylogenetic relationships, diversification patterns, distributional data, and general ecology in the Andean biota, large gaps in our understanding remain, particularly in the synthesis across scales. To fill these gaps, I aimed to explore patterns and processes that underlie species diversification in birds of the tropical Andes of South America by combining different approaches using phenotypic, phylogenetic, and genomic data in multiple temporal and spatial scales.

In the first chapter, I examined the macroevolutionary patterns of …

Implementation Of A Forensic Ancestry Inference Indel Panel, Jacqueline Molina

Student Theses

Ancestry-informative markers (AIMs) are genetic variants that exhibit significant frequency differences between populations, making them valuable tools for inferring biogeographical ancestry in forensic investigations. Insertion/deletion polymorphisms (INDELs) offer particular advantages for degraded forensic samples due to their short amplicon sizes and binary allelic nature. As forensic laboratories adopt newer instrumentation, validation of established assays becomes critical to ensure analytical continuity and reliability. This study evaluated the comparative performance of the SeqStudio™ Genetic Analyzer in detecting a 46 AIMs INDEL multiplex panel, previously established with the ABI 3130 Genetic Analyzer. Four commercial blood samples were analyzed using both platforms to assess …

Exploring Variability Of The Cg18562578 Methylquant Assay For The Forensic Discrimination Of Monozygotic Twins, Sydney E. Arnold

Student Theses

Monozygotic (MZ) twins possess identical DNA sequences, posing a problem for forensic scientists, as they are incapable of distinguishing MZ twins from each other using traditional DNA identification methods. However, the epigenomes of MZ twins will differ and might be used for their forensic discrimination. Here, we explored the variability of an assay previously developed by our laboratory that showed high discrimination potential for MZ twins using buccal swab DNA, cg18562578 MethylQuant. We measured precision at each step: bisulfite conversion, nested PCR, and qPCR, reproducibility, and repeatability. DNA methylation ratios were compared between two analysts carrying each step using the …

Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang

Dissertations, Theses, and Capstone Projects

Gliomas are the most devastating adult brain tumors characterized by poor survival rate and limited options for treatment. Previous studies have shown that they are very heterogeneous and can be further sub-classified based on their transcriptional signature and the presence of specific mutations. One such subtype, is the “proneural glioma”, which is characterized by the enrichment in oligodendrocyte progenitor cell (OPC) transcripts and mutations in genes encoding for the tumor suppressor P53 (Trp53) and for Platelet Derived Grow Factor (PDGF) signaling. Since OPCs are the most abundant proliferative population in the adult brain, in this …

Individual, Social, And Environmental Factors Associated With Patterns Of Parasitic Infection In Capuchin Monkeys (Cebus Imitator), Megan C. Henriquez

Dissertations, Theses, and Capstone Projects

Parasites, and the infectious diseases they carry, are thought to have significantly impacted our evolutionary trajectory for millennia. Exploring how parasites are acquired and transmitted by their hosts in wild, natural populations is integral to understanding how similar processes may have shaped host-parasite co-evolutionary relationships over time. However, parasitological studies in humans and in non-human primates have produced inconsistent results, highlighting the dynamic, nuanced, and unique relationships individual parasites have with their hosts. These relationships are largely regulated by variation in factors at host, social, and environmental levels. Characteristics unique to the host (e.g., age and sex), factors pertaining to …

In The Quest For New Horizons: Evaluating Novel Therapeutic Approaches For Tuberculosis Treatment, Selassie Mawuko, Aminata Traore, Bibi-Sakeena Khemraj, Anna Steto, Richa Gupta

Publications and Research

Tuberculosis (TB) in humans, caused by Mycobacterium tuberculosis, is a significant global health concern, resulting in high disease burden and mortality each year which together make it the world’s topmost infectious killer. The emergence of multidrug-resistant tuberculosis (MDR-TB) in recent decades has further exacerbated the present situation and warrants an urgent need to develop and investigate innovative treatment regimes. This study aims to assess the therapeutic potential of newly identified drug candidates, namely Bedaquiline, Delamanid, and Linezolid, in treating MDR-TB. We adopted a consolidated and integrated approach encompassing a thorough literature review, empirical experimental studies, multiple sequence alignments, and …

The Role Of Elongin B In Drosophila Melanogaster Muscle Development, Madelyne Dayan

Student Theses and Dissertations

Muscle atrophy is a result of a number of muscle diseases, as well as aging, disuse, and infections. Muscles weakened in these ways exhibit a characteristic decrease in size, strength, and mobility. The similarities between muscle in humans and Drosophila allow for direct comparisons to be made in vertebrates from studying muscle in Drosophila. Differential gene expression has been shown to play an important role in embryonic muscle development in Drosophila melanogaster. A previous study identified Elongin B (EloB) to be involved in somatic muscle morphogenesis in Drosophila, with mutant embryos displaying severe muscle defects, including thin, mis-attached, and missing …

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Andrea Feria, Nyla Walbrook, Anisa Turaeva, Rebecca Spokony

Publications and Research

Crystal cells, a subset of Drosophila melanogaster hemocytes, are important for melanization, a crucial immune response. While the genetic regulation of crystal cell develop remains incompletely understood, this study investigates the functions of five candidate genes: ACXB, ACXA, Gp210, CG4390, and Cyp4s3; identidied through previous genome-wide association studies. Using the Gal4/UAS system along with RNA interference (RNAi), we exclusively knocked down each gene in third instar larvae and quantified crystal cell populations following heat shock-induced melanization. Our results imply that the knockdown of ACXB and ACXA significantly increased crystal cell counts in both sexes, suggesting these genes either act as …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …

Karyotyping As A Method To Verify Phylogenetic Relationships Among The Enneacanthus Species, Ophelia A. Anderson

Theses and Dissertations

The Enneacanthus genus consists of three species of freshwater fish endemic to eastern North America: E. obesus (Banded Sunfish), E. gloriosus (Blue Spotted Sunfish), and E. chaetodon (Black Banded Sunfish). Previous studies using molecular data suggest that E. obesus and E. gloriosus are more closely related, with E. chaetodon as the most distantly related species in the genus. This study investigates the phylogenetic relationship among the Enneacanthus species, using karyotype characteristics - chromosome number, morphology and fundamental number - as comparative metrics. Chromosome spreads were obtained from scale and gill epithelium samples collected between 1993 and 1994. Prepared slides …

Developing Coexpression Systems To Introduce Hydroxyproline Into Protein Engineered Collagen Peptides Utilizing Hydroxylase From Acanthamoeba Polyphaga Mimivirus, Jennifer Soldatich

Theses and Dissertations

A major challenge of developing collagen mimetic peptides (CMPs) by bacterial expression is to include hydroxyproline for biomedical applications. Coexpression of Prolyl-4-hydroxylase from A.mimivirus with CMPs was investigated. Additionally, four expression designs were created for potential applications in mammalian cells to utilize their natural ability of proline-hydroxylation by post-translational modification.

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 …

The Influence Of Environmental Change On Genetic Diversity Across Spatial And Taxonomic Scales, Connor M. French

Dissertations, Theses, and Capstone Projects

The spatial distribution of genetic diversity is of interest to biodiversity scientists and conservationists and is a fundamental metric of biodiversity. Genetic diversity patterns across spatial and taxonomic scales contain information about population and assemblage dynamics that can convey their resilience to environmental change. Ectotherms are especially linked to their environments and may be especially sensitive to fluctuations in the environment over time. Herein, I investigate global and regional patterns of genetic diversity in two groups of ectotherms, insects and lizards, to understand the relationship between environmental change and genetic diversity, from populations to assemblages. Overall, my research aims to …

The Seat Of Singular Gene Choice: Dissecting The Role Of Odorant Receptor Enhancer Elements That Lead To Mammalian Olfactory System Expression, Alessandro M. Rosa

Dissertations, Theses, and Capstone Projects

Odorant receptors (ORs) were first identified in 1991 and the initial data strongly suggested that ORs were part of a large superfamily of G-protein-coupled receptors. Within a few years of the discovery of the OR superfamily, it became clear that each OR allele was exclusively expressed in olfactory sensory neurons (OSN), and that this singular expression leads to cellular identity. Many studies over the past thirty years have sought to unlock the mysteries of the mechanism for monoallelic and monogenic OR gene activation and expression in OSNs, however no definitive model for singular gene expression has emerged.

Using a series …

Interleukin 24 Induces Apoptosis Through Glycogen Synthase Kinase-3 Beta Inactivation In Prostate Cancer Cells, Sual J. Lopez, Moira Sauane

Theses and Dissertations

Interleukin 24 (IL-24) is a tumor-suppressing protein currently in clinical trials. IL-24 induces cancer-specific apoptosis by activating endoplasmic reticulum (ER) stress and mitochondria dysfunction. We have previously demonstrated that IL-24 leads to apoptosis in cancer cells by protein kinase A (PKA) activation in human breast cancer cells. To further understand the mechanism by which IL-24 induces apoptosis, I analyzed the role of glycogen synthase kinase-3 (GSK3), a highly conserved and normally active serine/threonine kinase in cancer cells and downstream target of PKA. The work reported here provides direct evidence that GSK3 was inhibited following IL-24 treatment in human prostate cancer …

Metabarcoding The Mycobiome: An Analysis Of The Gut Mycobiome Of Babies, Daniel B. Colon, Jeremy Seto

Publications and Research

The human gut mycobiome (the fungus that lives in our gut) has been correlated with overall health and disease in humans. There are several factors that affect the human gut mycobiome including delivery method during birth (vaginal vs. c-section) and the presence or absence of antibiotics at birth. The mycobiome of 140 infants aged newborn to 18 months were tested using fecal samples from 3 different time periods (meconium, 6 months, 18 months). A total of 434 fecal samples were collected. A midwife or nurse collected the meconium samples while the child’s parents collected the samples at the 6-month and …

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Avian Symbionts Of Sulawesi: Identifying And Correlating Malaria Parasites And The Microbiome In Communities Of Endemic Avian Hosts, Rachael Joakim

Dissertations, Theses, and Capstone Projects

Since the evolution of complex organisms, there have been communities of symbionts inhabiting them. Thanks to the development of parallel sequencing techniques, DNA of entire microbial communities can be sequenced from a single sample. Some microbes can be parasitic in nature, such as Haemosporida, an order of eukaryotes causing malaria. While most symbionts form a more commensal host relationship in wild systems, host-symbiont dynamics can vary in pathogenicity based on biotic and abiotic factors. In vertebrates, microbial communities in the gut play a major role in host function, including immune responses to Haemosporida. Though this relationship is most commonly explored …