Molecular Genetics Commons^™

Phylogeography, Fungal Host Specificity, And Fitness In The Corallorhiza Maculata Species Complex, Hana Thixton-Nolan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Mycoheterotrophic plants exploit fungi for most or all nutritional needs, providing a compelling system to address the evolutionary consequences of genome reduction, population-level variation, and germination requirements. I am using the widespread Corallorhiza maculata species complex to address questions of genomic variation, fungal host specificity, morphological variation, and germination requirements across the broad geographic range from Mexico to northern North America. This complex contains C. bulbosa, C. macrantha, and C. mertensiana, the latter with three varieties (maculata, occidentalis, and mexicana). These taxa vary in flowering time, floral morphology, and fungal associations. However, the degree …

A Balancing Act: Microrna Mediated Insect-Bacterial Homeostasis And The Tsetse Fly, Mason Hubbard Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

Microbial symbioses are ubiquitous across all kingdoms of life with broad and diverse impacts on the evolution of species. The sum of all microbes living in, on, or otherwise in close association with a host form the microbiota. In some cases, the development of a stable microbial association seems to have been necessary for the specialization of diet, as can be observed in numerous insect species, especially wood-eating, sap-feeding, and blood-feeding organisms. For the medically and economically tsetse fly (family Glossinidae), the mutualistic bacteria Wigglesworthia glossinidia is required for proper reproduction and supplementation of nutrients that the fly does not …

The Function Of Protein Glutamylation In Vision, Rawaa Aljammal

Graduate Theses, Dissertations, and Problem Reports (ETD)

Posttranslational glutamylation of protein has emerged as a novel candidate for cellular integrity. In a dynamic process, Tubulin Tyrosine Ligase Like proteins (TTLLs) introduce glutamate groups to their substrates, while Cytosolic Carboxypeptidases members (CCP1-CCP6) remove these glutamate groups. The outcome of this interplay is a wide range of substrates; each is glutamylated to a level crucial for its function.

Protein glutamylation is particularly abundant in neurons and in the axoneme of cilia and flagella. This distribution, along with the correlation between imbalanced glutamylation levels and compromised cellular functions, underscores the significance of protein glutamylation in maintaining cellular viability. However, the …

Investigating Birds As Dispersal Vectors Of Litylenchus Crenatae Subsp. Mccannii (Anguinidae), The Nematode Associated With Beech Leaf Disease, Spencer Rock Parkinson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Beech leaf disease (BLD) is an emerging forest pathogen primarily affecting American beech (Fagus grandifolia, Ehrh.) in North America and has been attributed to tree mortality of sapling sized trees within five to seven years of infection. Symptoms typically occur in regenerating American beech thickets sprouting from roots of trees killed by beech bark disease. Scientists first observed BLD in Ohio in 2012 and currently has spread to 15 states in the USA and one Canadian province. The nematode Litylenchus crenatae subsp. mccannii (Lcm) is highly associated with BLD symptoms, interveinal chlorosis and defoliation of leaves, and is currently …

Structural And Functional Consequences Of Pde6 Prenylation In Rod And Cone Photoreceptors, Faezeh Moakedi

Graduate Theses, Dissertations, and Problem Reports (ETD)

Phosphodiesterase-6 (PDE6) serves as a pivotal component in the phototransduction pathways of both cone and rod photoreceptors. In cones, PDE6 consists of tetrameric subunits: inhibitory (γ') and catalytic (α'). The catalytic subunit, PDE6α', contains a C-terminal prenylation motif. Deletion of this motif is associated with achromatopsia (ACHM), a form of color blindness. The mechanisms underlying the disease and the roles of PDE6 lipidation in vision remain elusive. Meanwhile, rod PDE6 is composed of α and β catalytic subunits and γ inhibitory subunits, with alterations in the C-terminal "prenylation motif" of PDE6β linked to retinitis pigmentosa (RP) pathology. In this comprehensive …

Extension Of The Ergot Alkaloid Gene Cluster, Samantha Joy Fabian

Graduate Theses, Dissertations, and Problem Reports (ETD)

Specialized metabolites produced by fungi impact human health. A large portion of the pharmaceuticals currently on the market are derived from metabolites biosynthesized by microbes. Ergot alkaloids are a class of fungal metabolites that are important in the interactions of environmental fungi with insects and mammals and also are used in the production of pharmaceuticals. In animals, ergot alkaloids can act as partial agonists or antagonists at receptors for 5-hydroxytryptamine (serotonin), dopamine, and noradrenaline as ergot alkaloids have chemical structures similar to those neurotransmitters. Therefore, they affect insects and mammals that consume them and can be used to produce drugs …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …

Elucidation Of The Role Of Agouti-Signaling Protein Throughout Folliculogenesis And Early Embryonic Development In Cattle, Heather L. Chaney

Graduate Theses, Dissertations, and Problem Reports (ETD)

The oocyte expresses certain genes during folliculogenesis to regulate the acquisition of oocyte competence. Oocyte competence, which refers to the presence of imperative molecular factors in the oocyte that are critical for high oocyte quality, is directly related to the ability of the oocyte to result in a successful pregnancy following fertilization. Over the past few decades, the development and optimization of assisted reproductive technologies, particularly in vitrofertilization, have enabled the beef and dairy industries to advance cattle genetics and productivity. However, only approximately 40% of bovine embryos will develop to the blastocyst stage in vitro. In addition, bovine embryos …

The Investigation Of Novel Bovine Oocyte-Specific Long Non-Coding Rnas And Their Roles In Oocyte Maturation And Early Embryonic Development, Jaelyn Zoe Current

Graduate Theses, Dissertations, and Problem Reports (ETD)

Early embryonic loss is a significant factor in livestock species' infertility, resulting in an economic deficit. In cattle, the in vivo fertilization rate is ~90%, with an average calving rate of about 55%, indicating an embryonic-fetal mortality rate of roughly 35%. Further, 70-80% of total embryonic loss in cattle occurs during the first three weeks after insemination, particularly between days 7-16. Growing evidence indicates that the oocyte plays an active role in regulating critical aspects of the reproductive process required for successful fertilization, embryo development, and pregnancy. However, defining oocyte quality remains enigmatic. Recently, many have abandoned the notion that …

Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports (ETD)

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …

The Receptor Basis Of Serotonergic Modulation In An Olfactory Network, Tyler Ryan Sizemore

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neuromodulation is a nearly ubiquitous process that endows the nervous system with the capacity to alter neural function at every level (synaptic, circuit, network, etc.) without necessarily adding new neurons. Through the actions of neuromodulators, the existing neural circuitry can be adaptively tuned to achieve flexible network output and similarly dynamic behavioral output. However, despite their near ubiquity in all sensory modalities, the mechanisms underlying neuromodulation of sensory processing remain poorly understood. In this dissertation, I address three main questions regarding the mechanisms of one modulator (serotonin) within one sensory modality (olfaction). I begin by establishing a "functional atlas" of …

Effects Of 4-Methylcyclohexanemethanol On Stress Response Pathway Regulators, In Saccharomyces Cerevisiae, Suk Lan Ser

Graduate Theses, Dissertations, and Problem Reports (ETD)

Hydrotropes are small molecules capable of inducing liquid-liquid phase separation by altering the solubility and conformation states of organic compounds that are increasingly becoming important in organizing chemical reactions and regulating complexes. They prevent protein aggregation causing these proteins to form condensates. Mediator, a highly conserved multi-subunit complex, plays an important role in transcription. Med15, a subunit found within the tail domain of the Mediator complex, works with stress-induced transcription factors and is regulated by many kinases, including CDKs and the AMP kinase, Snf1. Living cells respond by changing molecular and cellular pathways when they are exposed to stressful conditions. …

Evidence Of Y Chromosome Long Non-Coding Rnas Involved In The Radiation Response Of Male Non-Small Cell Lung Cancer Cells, Tayvia Brownmiller

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-small cell lung cancer (NSCLC) is the number one cause of cancer related mortality in the United States and worldwide. Advanced and therapeutically resistant lung tumors contribute to the high rate of mortality from NSCLC, therefore there is a need for new methods of diagnosing and treating this disease. Long non-coding RNAs (lncRNAs) have been shown to be a crucial component of human molecular biology, regulating nearly every cellular pathway from chromatin condensation to transcription and translation. Furthermore, many lncRNAs have been classified as oncogenes or tumor suppressors, highlighting the various molecular mechanisms they are involved in regarding the formation …

The Exploration Of Nanotoxicological Copper And Interspecific Saccharomyces Hybrids, Matthew Joseph Winans Phd

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanotechnology takes advantage of cellular biology’s natural nanoscale operations by interacting with biomolecules differently than soluble or bulk materials, often altering normal cellular processes such as metabolism or growth. To gain a better understanding of how copper nanoparticles hybridized on cellulose fibers called carboxymethyl cellulose (CMC) affected growth of Saccharomyces cerevisiae, the mechanisms of toxicity were explored. Multiple methodologies covering genetics, proteomics, metallomics, and metabolomics were used during this investigation. The work that lead to this dissertation discovered that these cellulosic copper nanoparticles had a unique toxicity compared to copper. Further investigation suggested a possible ionic or molecular mimicry …

Characterization Of Nodule-Specific, Slac And Mate Membrane Transporters In Medicago Truncatula, Lina Yang

Graduate Theses, Dissertations, and Problem Reports (ETD)

Legumes play a crucial role in sustainable agriculture because of their intrinsic ability to reduce atmospheric N₂ into NH₃ via symbiotic nitrogen fixation (SNF). SNF is carried out in the symbiosome, a quasi-organelle containing endosymbiotic rhizobial bacteria in the cytoplasm of infected cells of the nodule. Therefore, the bacteria are surrounded by a symbiosome membrane (SM), which is derived from the plant plasma membrane during infection. SNF requires constant nutritional exchanges between symbionts, including reduced carbon (dicarboxylates) from the plant for reduced nitrogen (NH₄⁺) from the bacteroids. This exchange of nutrients and signals is fundamental …

Genetic Regulation Of The Elicitation Of Glyceollin Biosynthesis In Soybean, Md. Asraful Jahan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Glyceollin phytoalexins are the pathogen-elicited defense metabolites that belong to the isoflavonoid family of molecules of soybean (Glycine max L. Merr). Phytophthora root and stem rot of soybean caused by Phytophthora sojae is a destructive disease throughout the soybean-growing regions worldwide causing devastating economic damages (globally $1-2 billion and over $250 million in the USA) every year. Engineering soybean plants that produce higher levels of glyceollins could confer resistance against this pathogen. Glyceollins also show anticancer and neuroprotective activities in mammals, therefore they are important for agriculture and medical research. Firstly, we were interested in understanding how biotic and …

Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …

Enhancing Water Stress Tolerance In Floriculture Crops, Suejin Park

Graduate Theses, Dissertations, and Problem Reports (ETD)

Water deficit is one of the major constraints on plant growth and development, causing reduction of crop productivity. To minimize water loss, among many adaptation strategies, plants close their stomata to reduce transpiration. The stomatal closure is regulated by light, internal CO2 concentration, and plant hormones, mainly abscisic acid. Plants’ response mechanisms to water deficit are complex processes involving numerous genes and various signaling pathways. Floriculture crops are often exposed to water deficit during shipping and retailing, and these periods often result in damaged crops and profit loss. Understanding of plant responses to water deficit stress will provide us an …

Effects Of Commercial Formulations Of Glyphosate On Saccharomyces Cerevisiae, Apoorva Ravi Shankar

Graduate Theses, Dissertations, and Problem Reports (ETD)

Commercial formulations of glyphosate are among the most extensively used herbicides around the world. The active ingredient, glyphosate, targets the aromatic amino acid pathway. This pathway is absent in mammals, resulting in low toxicity. Different formulations contain varying adjuvants and surfactants, whose synergistic effects are yet to be extensively studied at the cellular level. In this study, I tested multiple commercial formulations that showed a variation in growth phenotype among different yeast strains. To gain a better understanding of response and resistance mechanisms at the genome and transcriptome level, I carried out an in-lab evolution study, along with a transcriptome …

Association Genetics And Local Adaptation Of Populus Trichocarpa Torr. & Gray, Hari Bahadur Chhetri

Graduate Theses, Dissertations, and Problem Reports (ETD)

A major goal in plant science is overcoming the recalcitrance of plant biomass to cellulose extraction, to enable efficient production of cellulosic biofuel. We have started to understand the genetic basis of some important traits such as cell wall chemistry, but we do not know anything about the key structural and functional traits such as wood anatomy that greatly affect plant biomass recalcitrance. Furthermore, biofuel feedstocks have to be adapted to varied environmental conditions to ensure high productivity in plantations, but little is known about the molecular mechanisms underlying local adaptation. With the advancement in sequencing and genotyping technologies, association …

Seastar: Systematic Evaluation Of Alternative Transcription Start Sites In Rna, Zhiyi Qin, Peter Stoilov, Xuegong Zhang, Yi Xing

Faculty & Staff Scholarship

Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5′ Untrans- lated Regions (5′UTRs) and N-terminal coding se- quences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to iden- tify the 5′ ends of transcripts. We developed a compu- tational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and com- pares alternative first exon usage across multiple bi- ological conditions. The exons inferred by SEASTAR coincide with transcription start sites identified di- rectly by CAGE experiments and bear epigenetic hall- marks of active promoters. To …

Combining Semi-Synthesis With Plant And Microbial Biocatalysis: New Frontiers In Producing A Chemical Arsenal Against Cancer†, Samuel Gary, Janet Adegboye, Brian Popp, Jean-Christophe Cocuron, Brooklyn Woodrum, Nik Kovinich

Faculty & Staff Scholarship

Natural products (NPs) that exhibit anticancer activities are frequently not potent enough to be used clinically as therapeutics. Semi-synthesis and metabolic engineering are promising approaches for producing more efficacious derivatives of anticancer NPs (ACNPs), but each technique alone can be inefficient at obtaining specific ACNP derivatives that may be suspected to have enhanced anticancer activity. Here, we demonstrate that the methods of semi-synthesis and biocatalysis can be used as modules in succession and in different combinations to produce 6,8-dibromogenkwanin, a derivative of the ACNP apigenin. Further, we demonstrated that soybean seed coats can be used as a biocatalyst to convert …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …