Genetics and Genomics Commons^™

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 …

Conservation, Comparative Genomics And Species Delimitation Of The Reindeer Lichens (Cladonia), Jordan R. Hoffman

Dissertations, Theses, and Capstone Projects

The genus Cladonia represents one of the most speciose genera of lichenized fungi, with more than 500 known species encompassing a diverse array of morphologies and habits. These lichens form keystone species in many habitats, serving a variety of ecological roles. However, despite being among of the more well studied lichens, there is much still unknown or under-studied about them. As is the case with most lichen study systems, phylogenetic study has been limited to a small number of partial loci, while adoption of next-generation sequence methods has been slow. As a consequence, there are still knowledge gaps in Cladonia …

Informed Consent: Foundations And Applications, Joanna Smolenski

Dissertations, Theses, and Capstone Projects

Since its advent in the 20th century, informed consent has become a cornerstone of ethical healthcare, and obtaining it a core obligation in medical contexts. In my dissertation, I aim to examine the theoretical underpinnings of informed consent and identify what values it is taken to protect. I will suggest that the fundamental motivation behind informed consent rests in something I’ll call bodily self-sovereignty, which I argue involves a coupling of two groups of values: autonomy and non-domination on the one hand, and self-ownership and personal integrity on the other. I will then go on to consider two 'case …

Investigation Of Notch Signaling In Cone Fate Specification In Vertebrate Retina, Xueqing Chen

Dissertations, Theses, and Capstone Projects

In the vertebrate retina, cone photoreceptors are crucial for high acuity color vision. Several retinal diseases lead to loss of cones and there is a need to identify the normal developmental genesis of these cells to inform the development of stem cell-based therapies. Cone genesis has previously been shown to be repressed by Notch signaling, however, the mechanism by which Notch signaling controls cone fate determination is still unclear. It has been identified that cone photoreceptors are formed from multipotent retinal progenitor cells (RPCs) that first generate genetically-defined, restricted RPCs with limited mitotic and fate potential to preferentially form cones …

Molecular Mechanisms Underlying Cell Fate Choice Within Specific Retinal Lineages, Estie Schick

Dissertations, Theses, and Capstone Projects

During development, retinal progenitor cells (RPCs) divide to form all of the cell types that make up the retina. Multipotent RPCs are competent to generate all retinal cell types, while restricted RPCs form specific lineages of cells. In particular, one genetically-defined RPC type preferentially gives rise to cone photoreceptors and horizontal cells. Many of the mechanisms that are responsible for directing cell fate choice within this lineage are unknown. This thesis largely focuses on examining the development of specific cell types and subtypes from restricted RPCs and on investigating the gene regulatory events that underlie cone photoreceptor and horizontal cell …

Microbial-Host Dynamics And The Evolution Of Nearshore Diversity In Hippocampus Abdominalis, Jimiane L. Ashe

Dissertations, Theses, and Capstone Projects

Local adaptation is a fundamental concept at the core of evolutionary process. Devising means to break down larger concepts and systematically test internal mechanisms are key to understanding the driving forces behind the influence of environmental differences on biological systems. To understand dynamic processes in the natural world, we must strip away layers and confounding variables that may mask the signal we hope to understand. In this case seahorse species, Hippocampus abdominalis, or the pot-bellied seahorse, made an unlikely but ideal study system. The first layer to strip away was neutral genetic variation within the population. A multilocus genetic …

The Role Of Placental Genes On Intellectual Disability And Developmental Delay, Maedot A. Yidenk

Dissertations, Theses, and Capstone Projects

The complex interaction between gene expressions and environmental factors plays a key role in the pathogenesis of various diseases, including neurodevelopmental disorders (Lenroot & Giedd, 2008). This study aimed to evaluate first, the magnitude of association between placental gene Methyl-CpG Binding Protein 2 (MeCP2) and intellectual disability (ID) in the offspring and second, the synergy between placental gene Forkhead box protein 1(FOXP1) and developmental delay (DD) in the offspring. We focused on assessing two specific paradigms, i) placental gene expressions of MeCP2 among children that have ID vs. children without ID; and ii) placental gene expression of …

Evolution And Development Of The Seed Coat In Gymnosperms, Cecilia Zumajo

Dissertations, Theses, and Capstone Projects

Gymnosperms and angiosperms are the most abundant plant lineages on earth and constitute a turning point in the evolution of plants because they are at the origin of the seed, a key morphological and developmental novelty in the evolution of land plant. Although the morphological variation of the seed, across seed plants, may on its own, explain the complexity of this structure, the origin, and evolution are even more, the understanding of these topics is still under discussion. Evidence shows that previous studies have often lacked the component of gene expression, particularly in species that are not model species. The …

Genomic And Ecological Dimensions Of Malagasy Reptile And Amphibian Biodiversity, Arianna L. Kuhn

Dissertations, Theses, and Capstone Projects

A long history of isolation coupled with complex topographic and ecological landscapes makes Madagascar ideal for exploring the historical factors that have shaped patterns of population diversity and endemism. Many species-level studies have suggested Late Quaternary climate change may have influenced population dynamics in the tropics, but Madagascar’s ecologically unique biomes or individual species properties may have driven idiosyncratic responses to these shifts. Using community-scale population genetic data I implement a hierarchical approximate Bayesian computation (hABC) approach to evaluate the degree of synchronous population expansion during glacial cycles across herpetofaunal assemblages both within and across discrete biomes and taxonomic groups. …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …

Regulation Of A Messenger: Raising Oskar, It Takes A Village, Livia V. Bayer

Dissertations, Theses, and Capstone Projects

D. melanogaster oogenesis serves as an excellent system to study the life of an mRNA. Tremendous work has been done to understand the numerous complex mechanisms of mRNA regulation, still there is still so much that is yet to be discovered. In this thesis, I present studies I carried out to address several aspects of oskar mRNA post-transcriptional regulation. Leading me to extend our current understanding of the carefully controlled regulation of oskar mRNA life cycle via a myriad of proteins. I found that a specific NPC component, Nup154 is necessary not only for its export from the nucleus, but …

Employing High Probability Gene Choice Elements To Understand Singular Odorant Receptor Expression, Raena Mina

Dissertations, Theses, and Capstone Projects

The ability to detect odorous chemicals in the environment is the oldest of the senses necessary for survival, from escaping danger, finding mates, to locating food. It is said that humans can identify and discriminate up to a trillion different odor mixtures. For chemoreception to have such a high discriminatory power, would require a diverse population of cells dedicated for odor detection. These detector cells are the olfactory sensory neurons (OSNs), which express odorant receptors (ORs) that bind to chemical odors in the environment. In order to increase specificity and sensitivity, an essential property in olfaction is for each OSN …

Dietary Development And Nutritional Ontogeny In Gorilla Beringei : A Multi-Layered, -Omics Approach, Emma C. Cancelliere

Dissertations, Theses, and Capstone Projects

In species who consume folivorous diets, immature individuals must contend with the challenges of extracting nutrients from fibrous foods before dietary adaptations and strategies are fully developed. Additionally, immatures have distinct nutritional needs to support their stage-specific metabolic and biophysiological requirements. To meet these stage-specific needs, while constrained by underdeveloped feeding strategies and digestive capacities, immatures may adopt distinct diets better suited to their specific developmental context. However, where dietary modification is constrained by low dietary diversity or landscape homogeneity, it is unclear how immature individuals compensate through alternative strategies. In turn, little is known about the nutritional and life …

Molecular Roles Of Small Inner Membrane Proteins In Escherichia Coli Cell Envelope Integrity, Aaron Mychack

Dissertations, Theses, and Capstone Projects

The biological membrane is an essential, defining feature of all cells. Biological membranes comprise phospholipid bilayers as well as a complement of proteins which are unique to a given organism. These proteins play a central role in dictating the biochemical state of the cell’s internal cytoplasm by controlling selective passage of solutes in and out of the cell, transducing signals in response to extracellular stimuli, and controlling the biogenesis of the bilayer itself which is critical towards barrier function. For most bacteria, the periphery of the cell is multi-layered, including both a biological membrane as well as a peptidoglycan cell …

Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori

Dissertations, Theses, and Capstone Projects

The diverse neuronal cell types in the vertebrate retina all originate from multipotent retinal progenitor cells (RPCs). These undergo a series of molecular changes driven by developmental gene regulatory networks (GRNs) as they divide to generate RPCs which are more restricted in their potential fates. It is crucial to understand these GRNs and changes to gene expression in order to understand how cell identity is established during retinal development. In particular, the GRN that promotes the development of cone photoreceptors and horizontal cells is not well-defined. This work focuses on two approaches to further elucidate the components of this regulatory …

Probing The Limits Of Singular Gene Expression Through The Activity Of High Representation Odorant Receptor Transgenes, Eugene Lempert

Dissertations, Theses, and Capstone Projects

Singular gene expression is a common phenomenon in biology, making its appearance in immunoglobulin selection, protocadherin expression, X chromosome-inactivation, random monoallelic expression, and olfactory receptor choice. Singularity involves an activation and a feedback step. The mechanisms of singular gene choice have some capacity to integrate additional member genes while still maintaining singularity, but will activate an additional member if an earlier choice was incapable of triggering the feedback step. Odorant Receptor (OR) genes are substantially divergent from each other in terms of coding sequence, promoter structure, and genomic locus, all of which plays a role in how many Olfactory Sensory …

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 …

On The Distribution Of Genetic Variation In Ecological Communities, Isaac Overcast

Dissertations, Theses, and Capstone Projects

Biodiversity in ecological communities is structured hierarchically across spatial and temporal scales. Many open questions remain as to how this structure accumulates. For example, what are the relative contributions of dispersal versus in situ speciation? Or, how important are stochastic drift versus deterministic processes? Up to this point, these questions have been investigated by isolated disciplines (e.g. macroecology, comparative phylogeography, macroevolution) using tools and data that tend to focus on only one axis of community scale data (e.g. phylogenies, relative abundances, and/or trait information). Yet we know that there are feedbacks among processes that respond on short, medium, and long …

Tamalin/Gras-1 Connects Glutamate Receptor Activity To The Insulin/Igf Signaling Cascade To Regulate Neuroprotection In A Nematode Model Of Excitotoxicity, Ayesha Chowdhury

Dissertations, Theses, and Capstone Projects

Brain ischemia is a major cause of debilitation and death in the United States. Excitotoxicity, a condition that arises from the accumulation of glutamate (Glu) in the synapse that leads to overactivation of Glu receptors (GluRs), is the major mechanism of neuronal damage in brain ischemia / stroke. Although it is commonly acknowledged that over activation of GluRs leads to neurodegeneration, it has been recently shown that even during excitotoxicity Glu has a concurrent important role in regulating neuroprotection. GluR-activated transcription factors seem to mediate this neuroprotection, but it remains unclear which signaling cascades and transcription factors are regulated by …

Towards A Mathematical Model Of Motility Using Dictyostelium Discoideum: Proteins And Geometric Features That Regulate Bleb-Based Motility, Zully Santiago

Dissertations, Theses, and Capstone Projects

A variety of biological functions depend on actin organization. The organization of actin is tightly regulated by a plethora of extracellular and intracellular signaling, scaffolding, and actin-binding proteins. Dysfunctions in this regulation lead to immune diseases, increased susceptibility to pathogens, neurodegenerative diseases, developmental disorders, and cancer metastasis. A variety of actin-dependent processes, including cell motility, are regulated by several proteins of interest: Paxillin, a scaffolding protein; WASP, an actin nucleating protein; SCAR/WAVE, another WASP family actin nucleating protein; Talin, a cortex-to-membrane binding protein; Myosin II, an F-actin contracting motor protein; and Protein Kinase C, a protein kinase. D. discoideum cells …

Eugenics In The 21st Century, Jessica Linn Chin

Dissertations, Theses, and Capstone Projects

Eugenics is the science of enhancing the human population through the management of breeding and hereditary traits. This thesis explores the history of eugenics and shows how eugenic practices continue in the 21^st century with advancements in technology and positive eugenic goals that can result in adverse effects on the human body and society. When Sir Francis Galton coined the term eugenics in 1883, he intended to improve British society with the use of positive eugenics. Galton used positive eugenics to encourage people with good mental and physical qualities to produce more children. He avoided negative eugenics, which involved …

A Novel Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Synapse Development, Hao Wu

Dissertations, Theses, and Capstone Projects

Cytoskeleton based active transport with motor proteins is essential for mRNA localization and local protein translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased screen for interaction between mRNA binding proteins (RBP) and motor proteins, we identified protein interacting with APP tail 1 (PAT1) as a potential direct adapter between the β-actin mRNA Zipcode-binding protein 1 (ZBP1) and Kinesin-1 motor complex.

Mouse PAT1 is similar to the Kinesin Light Chain (KLC) in amino acid sequence and binds directly to KLC. High-resolution images from structured illumination microscopy (SIM) indicates that synaptic stimulation …

Racial Becoming: How Agentic (Self-Initiated) Encounter Events Inform Racial Identity Refinement, Devin A. Heyward

Dissertations, Theses, and Capstone Projects

Racial identity literature has typically focused on identity formation through a series of stages. It also has centered how the experience of negative encounter events informs racial identity formation. With the advent of new genealogical and genomic technology, it is imperative to expand the focus of identity literatures to include encounter events, which participants elect to experience (i.e. self-initiated or agentic encounter events). By using this frame, identity processes become fluid and informed by individual life experiences. In the context of this study, direct to consumer genetic ancestry tests (DTC-GAT) are operationalized as a self-initiated encounter event. Participants were …

The Role And Regulation Of Alternative Polyadenylation In The Dna Damage Response, Michael R. Murphy

Dissertations, Theses, and Capstone Projects

Cellular homeostasis is achieved by the dynamic flux in gene expression. Post-transcriptional regulation of coding and non-coding RNA offers a fast method of adapting to a changing cellular environment, including deadenylation, microRNA (miRNA) pathway, and alternative polyadenylation (APA). In this dissertation, I explored some of the mechanisms involved in the post-transcriptional regulation of gene expression. The main hypothesis in these studies is that a single APA event after DNA damage is governed by specific conditions and factors outside of current known regulators of APA, and that the resultant transcript has a role in the DNA damage response (DDR). My aims …

Distribution And Population Structure Of The Invasive Nitellopsis Obtusa (Desv. In Loisel.) J. Groves And Native Species Of Characeae In The Northeast U.S.A., Robin Sleith

Dissertations, Theses, and Capstone Projects

Freshwater ecosystems are some of the most biologically diverse environments on Earth. Billions of humans rely on functioning freshwater ecosystems for drinking water and many other services. These ecosystems are increasingly threatened by human impacts including nutrient pollution, invasive species, and climate change. Here I contribute four research chapters that investigate freshwater diversity and ecosystem threats using the Characeae, a family of freshwater green macroalgae, as a study system. Characeae are a diverse and ancient group with more than 500 extant species and a fossil history spanning at least 250 million years. These algae are macrophytes in freshwater ecosystems, and …

Characterization Of Immunomodulatory Microbial Factors In Medicinal Plants, Kriti Kalpana

Dissertations, Theses, and Capstone Projects

Medicinal plants are one of the biggest sources of natural products with therapeutic importance. There are currently over 28,000 plants with putative medicinal values. Plant-derived compounds have been explored extensively for various biological activities ranging from anti-cancer, immune-boosting to anti-inflammatory and anti-oxidant. Some of the most important therapeutic agents are of plant-origin, such as paclitaxel from Pacific yew (Taxus brevifolia) and artemisinin from qinghao su (a Chinese medicinal herb; a.k.a. Artemisia annua) to name a few.

The study presented in this thesis started out as classical pharmacognosy research, which focused on the identification of immunostimulatory factors in …

Underlying Contribution Of Executive Functioning To Cognition And Academic Achievement In Individuals With Dystrophinopathy, Robert Fee

Dissertations, Theses, and Capstone Projects

Dystrophinopathy is a genetic disorder that results in the lack of or abnormal expression of the protein dystrophin. It is a disorder that alters cell structure and function, impacts the developing brain and brain function, presents with multi-domain cognitive deficits, and influences both mood and behavior. Cognitive impairments appear to be more localized to specific areas of functioning rather than a global deficit; however, deficits have been identified across multiple cognitive domains including language and aspects of executive functioning. A careful examination of the cognitive phenotype and its association to mutations affecting CNS isoforms is necessary to clarify the neuropsychological …

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 …

A Contribution Toward A Global Monograph Of Gyroporus: Taxonomy, Phylogeny, Biogeography, Naveed Davoodian

Dissertations, Theses, and Capstone Projects

Gyroporus (Sclerodermatineae, Boletales, Agaricomycetes, Basidiomycota, Fungi) is a genus of ectomycorrhizal mushroom-forming fungi distributed throughout the world in suitable habitats. Previous attempts to untangle the diversity of this genus proved difficult due to the presence of semi-cryptic species and equivocal results from phylogenetic analysis of ribosomal RNA markers. To overcome these obstacles, a combined taxonomic and phylogenetic (emphasizing protein-coding genes) approach is used here to delimit species and elucidate geographic and evolutionary patterns of Gyroporus. Careful study of relevant literature and herbarium specimens was augmented by field work in North America, Australia, and East Asia for observation and collection …