Life Sciences Commons^™

Mechanistic Examination Of Protist-Mediated Plant Growth Through The Comparative Development Of Medicago Truncatula, Shane Connolly

University Scholar Projects

Protists are known to increase plant growth through two main mechanisms: the microbial loop and the alteration of the root microbiome. The microbial loop is a nutrient recycling method in which protists provide inorganic nitrogen ions to the plant. Alteration of root microbiome leads to the removal of plant pathogens and shifting communities towards plant growth-promoting bacteria (PGPB). This study aimed to elicit which mechanism could produce the largest boost in shoot weight for Medicago truncatula. A series of microcosm experiments were explored in which M. truncatula was grown with variable microbiome structures to allow for mechanism differentiation. The …

Cenabis Bene: A Culinary Odyssey Through Apicius, Kathryn Atkinson

University Scholar Projects

Apicius is the sole surviving cookbook from classical antiquity; as such it is invaluable for what it tells us about ancient feasting customs. Yet the gluttony typically associated with classical antiquity has no place in Apicius beyond the art that is inherently associated with food; we are not so much given a seat at the cena (dinner) as we are led into the kitchen, handed an apron, and instructed to cook. This critical analysis explores each recipe not only on the surface—i.e., examining the ingredients and recreating selected recipes—but also on a deeper level, lifting food above its concrete reality …

Dynamic Transcriptomic Responses Of Circulating Immune Cells In Response To Subsequent Days Of Exercise Heat Stress, Soohyun Oh

University Scholar Projects

Acute exercise and chronic training have diverse effects on immune function that are still not well understood. There are remaining questions about how an acute bout of exercise, competition, or repeated training over a period affects an individual’s immune defense system. In a related study, there is evidence that acute exercise may serve as an adjuvant to enhance response to immune function as well as contradicting evidence, including our preliminary data (unpublished). Understanding the fundamental function and gene expression of circulating immune cells in response to acute exercise and in various contexts such as heat stress is critical in understanding …

The Effect Of Fibrodysplasia Ossificans Progressiva On The Tongue, Amy Backal, Amanda Harrop, David J. Goldhamer Dr.

University Scholar Projects

FOP is a rare genetic disorder in which skeletal muscle and associated connective tissue progressively turn to bone through a process called heterotopic ossification (HO). The extra skeletal bone growth is cumulative, eventually trapping patients in a second skeleton that eventually leads to death by asphyxiation. The FOP mutation is autosomal dominant that can be inherited or acquired sporadically. Unfortunately, FOP is currently incurable with no therapeutic options to inhibit bone growth or reduce existing bone nodules. My project intends to further our understanding of the cellular mechanisms of the disease within the tongue muscle. A population of cells known …

Identification Of Translesion Synthesis Inhibitors That Target Rev7/Rev3 Protein-Protein Interactions, Seema Patel

University Scholar Projects

Translesion synthesis (TLS) is a cellular mechanism utilized by cancer cells to tolerate DNA damage caused by chemotherapeutics, like cisplatin, by replicating past unrepaired lesions. This increases the rate of mutations, which leads to the emergence of drug-resistant cancer cells. Preliminary studies have shown that disrupting the protein-protein interactions (PPI) in the TLS heteroprotein complex increases cells’ sensitivity to first-line genotoxic chemotherapy, illustrating how inhibiting TLS assembly and function can significantly increase cancer cell death. These results underscore the therapeutic potential of targeting TLS PPI. My thesis focuses on identifying inhibitors capable of disrupting the Rev7/Rev3 TLS PPI. This study …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

University Scholar Projects

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Computational Investigations Into Binding Dynamics Of Tau Protein Antibodies: Using Machine Learning And Biophysical Models To Build A Better Reality, Katherine Lee

University Scholar Projects

Misregulation of post-translational modifications of microtubule-associated protein tau is implicated in several neurodegenerative diseases including Alzheimer’s disease. Hyperphosphorylation of tau promotes aggregation of tau monomers into filaments which are common in tau-associated pathologies. Therefore, tau is a promising target for therapeutics and diagnostics. Recently, high-affinity, high-specificity single-chain variable fragment (scFv) antibodies against pThr-231 tau were generated and the most promising variant (scFv 3.24) displayed 20-fold increased binding affinity to pThr-231 tau compared to the wild-type. The scFv 3.24 variant contained five point mutations, and intriguingly none were in the tau binding site. The increased affinity was hypothesized to occur due …

Foe To Friend: Parallel Domestication Of Ophiocordyceps From Fungal Parasite To Beneficial Symbiont In Cicadas, Jason Vailionis, Eric Rl Gordon, Chris Simon

University Scholar Projects

Nutritional symbioses are integral to the survival and diversity of many insects. The majority of herbivorous insects in the order Hemiptera possess stable, inherited symbionts that produce essential amino acids and vitamins. However, instability has been observed in cicadas, with one bacterial symbiont, Hodgkinia cicadicola, being repeatedly replaced by a new fungal symbiont, Ophiocordyceps. The fungal symbionts are thought to be derived from parasitic Ophiocordyceps species, but little is known about these parasitic ancestors or how the transition from parasite to mutualist occurs. We used a combination of targeted amplified genes and metagenomic sequencing to investigate the evolution …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Impact Of Angiogenic And Osteogenic Factors In The Presence Of Biodegradable Piezoelectric Films, Jayla Millender

University Scholar Projects

One of the most common causes of bone graft rejection is lack of a vascular network connecting the graft to the existing native tissue – allowing for nutrient flow. Under current grafting techniques, the existing blood vessel network in the patient slowly invades the implant in order to supply the injured site with its necessary nutrients. The purpose of this research is to determine if a synthetic bone graft with a stable microvascular network can be developed in vitro. I hypothesize that the use of indirect angiogenic factors such as sonic hedgehog homolog and hypoxia-inducible factor-1 in combination with the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Study Of A Putative Niche Adapting Operon In Microbes Inhabiting The Gut Of Blood Digesting Animals, Marlene Abouaassi

University Scholar Projects

The sialic acid utilization (SAU) operon is a horizontally acquired gene set that allows bacteria to utilize sialic acid as an alternate source of carbon and nitrogen in the guts of blood eating animals. Sialic acid often occurs as a terminal sugar in complex glycoproteins. It functions in cell signaling and adhesion. Sialic acid is an important component of the cellular envelope of animals. Some microorganisms have evolved to decorate their own surface with sialic acid to evade the host’s immune response (molecular mimicry). The SAU operon encodes enzymes that hydrolyze sialic acid from glycoproteins, transport sialic acid into the …

Detection Of Tinnitus In Cba/Caj Mice Using The Active Avoidance Shuttle Box Test, Grace Nichols

University Scholar Projects

Tinnitus is a neurological condition that involves the perception of a sound that is not actually there. Individuals affected with tinnitus describe the condition as a ringing, buzzing, or whooshing sound in their ears. One-third of the population is estimated to have tinnitus, and for many individuals, the condition negatively impacts quality of life. Difficulty falling asleep, trouble with hearing and concentrating, and in some cases, depression, have all been observed to occur with tinnitus.

Tinnitus has been extensively studied in animals, and behavioral tests are the primary method of evaluating the presence of tinnitus in animals. This study evaluates …

Genetic Analysis Of Flower Color Differences Between A Hummingbird-Pollinated And A Self-Pollinated Monkeyflower (Mimulus) Species, Caitlin Foster

University Scholar Projects

Flower color plays an important role in pollinator discrimination and speciation. Understanding the genetic contributions to flower color differences between two closely related species, Mimulus cardinalis and Mimulus parishii, can improve understanding of how they developed different pollination syndromes and diverged from a recent common ancestor. M. cardinalis is hummingbird-pollinated and has large, bright red flowers while M. parishii is self-pollinated and has small, pale pink flowers. An F2 hybrid population between these two species was created to establish a platform for analysis of the genetic architecture controlling the differences in anthocyanin pigmentation. Statistical analysis of anthocyanin concentration distribution …

Mechanisms Of Statin Effects On Muscle And Neuronal Proteostasis, Daniel Yu

University Scholar Projects

Statins are widely prescribed and used chronically, but we know little about the effects on long-term protein homeostasis during stress and aging. Our aim was to quantify the effect of statins on stress-induced protein damage. We administered atorvastatin in a dose-response curve in Caenorhabditis elegans under naïve control conditions and in conditions of hypertonic and heat stress known to induce muscle damage measurable as countable puncta in a polyglutamine aggregation model of damage. We observed that there is significant polyglutamine aggregation variability among worms at baseline and thus further study requires within experiment baseline controls, per worm. Our results are …

Reorganization Of The Human Ventricular-Subventricular Zone Neural Stem Cell Niche In Fetal-Onset Hydrocephalus, Saurabh Kumar

University Scholar Projects

Fetal-onset hydrocephalus is a relatively common birth defect occurring in 1-2 cases per thousand births and is characterized by abnormally expanded brain ventricles. Current diagnosis for this complex pathology often involves relatively simple metrics and heavy reliance on clinician experience over objective measures. Those affected often suffer chronic headaches and cognitive deficits and may present with a bulging skill. Shunting is considered the standard treatment for communicating hydrocephalus (i.e. cerebrospinal fluid flow is physically unobstructed in the ventricular system). Shunting remains a highly invasive procedure often performed during the critical period of infancy and has a high failure rate of …

Investigating The Neurobiology Of Motivational Deficiencies In Major Depressive Disorder: 5-Ht1b Receptor Involvement In Behavioral Effects Of Fluoxetine (Prozac), Sarah Ferrigno

University Scholar Projects

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) are the most commonly prescribed treatments for depression. Although efficacious for symptoms such as a depressed mood, SSRIs do not alleviate symptoms of amotivation, anergia, and fatigue. Furthermore, in clinical and preclinical studies, SSRIs have been shown to exacerbate motivational impairments and general fatigue. It is likely that fluoxetine-induced dysfunctions are due to overstimulation of one or more 5-HT receptors, with one possible candidate being the 5-HT_1B receptor. Therefore, the aim of the study was to evaluate the role of 5-HT_1BRs in fluoxetine-induced amotivation using a rodent behavioral …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

The Signaling Pathways Of Metallothionein-Mediated Chemotaxis In Breast Cancer, Jennifer Messina

University Scholar Projects

Metallothionein (MT) is a small, thiol rich protein released into the extracellular environment in response to stress. Elevated expression of MT has been linked to many inflammatory diseases including inflammatory bowel diseases, diabetes, and cancer. In breast cancer, high expression of MT has been associated with poor patient prognosis. Previous studies have shown that MT acts as a chemoattractant in lymphocytes, and that UC1MT, a monoclonal anti-MT antibody, can block this chemotactic response. In addition, it has been shown that both Cholera toxin and Pertussis toxin, which are known antagonists of G-protein coupled receptors, can inhibit MT-mediated chemotaxis. Here, I …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

Development And Ex Vivo Characterization Of Enteric Coated Chitosan Beads For Crohn’S Disease Management, Craig Mendonca

University Scholar Projects

Drug delivery is the process of transporting a drug to its site of action. It includes controlled delivery, where the drug is released at the tissue in a regulated manner. Additionally, it includes targeted delivery, where the drug is aimed at a specific tissue or region to avoid unwanted side effects (that would occur if the drug were distributed throughout the body). A cellulose acetate phthalate coated chitosan bead was developed as a formulation for controlled and targeted release of dexamethasone to the ilium and colon. This formulation was determined to be effective in delaying dexamethasone release until the formulation …

Effect Of Silk-Based Hydrogel Topography On Intestinal Epithelial Cell Morphology And Wound Healing In Vitro, Marisa E. Boch

University Scholar Projects

Recent advances in the field of biomaterials have suggested that cells cultured on substrates resembling the native tissue mechanical properties, matrix and growth factor composition, and topography can adopt phenotypes that more closely resemble the in vivo tissue compared to cells cultured on non-mimetic constructs. Understanding the effect of culture substrate on in vitro tissue formation is important for bioengineering applications that include mechanistic studies of healthy tissue function and development of disease models. In this work, Caco-2 adenocarcinoma cells were seeded on flat and crypt-like topographies of 3D-printed cytocompatible hydrogels derived from silk fibroin protein. Silk hydrogels were selected …

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …

Genotype-Specific Insertion Of Cytotoxic Genetic Elements Into Cancer Cells, Ryan Englander

University Scholar Projects

The new gene editing system CRISPR/Cas9, composed of a complex composed of a guide RNA and the Cas9 endonuclease, promises to revolutionize biological research and potentially allow clinicians to directly modify patient DNA in vivo. While its applications in the treatment of genetic diseases and in modifying immune cells for immunotherapy are currently being explored, CRISPR/Cas9’s potential utility as a modular system for targeting tumor-specific mutated sequences has not as of yet been explored. While CRISPR/Cas9 is specific enough to target small insertions and deletions or gross chromosomal rearrangements, it is not specific enough to reliably restrict editing to …

Investigation Of Bacteria From The Trachymyrmex Septentrionalis Fungus Garden For Potential Antibacterial Drug Leads, Brendan Stewart

University Scholar Projects

Bacterial and fungal strains are growing resistance to antibiotics and antifungal agents at an alarming rate. According to the Centers for Disease Control and Prevention, over two million people in the United States in 2016 were diagnosed with an infection resistant to antibiotics. As such, there has been increased interest in natural products as sources of novel compounds that are essential to the development of new drugs and treatment methods. Within the environment, there are various host-microbe symbioses, one of which is the Trachymyrmex septentrionalis leaf-cutter ant community. The microbes in symbioses like the T. septentrionalis community are hypothesized to …

The Role Of Sr-B1 In Lipid Metabolism And Inflammation In 3t3-L1 Adipocytes, Christina Jiang

University Scholar Projects

Obesity is associated with a number of complications that may increase the risk for chronic disease, including inflammation and dysfunctional high-density lipoprotein (HDL) particles. Scavenger receptor class B member 1 (SR-B1) is an HDL receptor found in the cell plasma membrane involved in cholesterol exchange and the initiation of intracellular signaling cascades. During the process of adipocyte (fat cell) formation (adipogenesis), there is a delicate balance of transcriptional programs that affect cholesterol transport and facilitate lipid accumulation. Mice fed a high fat diet have increased SR-B1 mRNA expression in adipose tissue depots. Furthermore, SR-B1 mRNA expression was significantly increased in …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Characterization Of Myod And Myf5 Double-Knockout Muscle Stem Cells During Muscle Development, Andreea Dinicu

University Scholar Projects

MyoD and Myf5 are transcription factors that regulate myogenesis by promoting satellite cell transcription. The two genes are known to display functional redundancy. Both genes are considered myogenic determination genes and are expressed in satellite cells. The fate of myogenic precursors in the absence of both MyoD and Myf5 remains largely unknown. We aimed to begin attaining this knowledge as part of this project. We utilized a CreLoxP system to control the expression of MyoD in mice lacking Myf5. MyoD was knocked out at embryonic day (E) 11.5 during myogenesis. Limbs were collected from experimental mice following tamoxifen injection. …

Comparison Of Feather Pigments In Red-Winged Blackbirds (Agelaius Phoenicus) Between Historical And Modern Samples, Genevieve Nuttall

University Scholar Projects

Coloration is vital to birds; it is involved in mating, territorial display, communication, camouflage, and predation. Birds rely on their environment for the raw materials necessary to make most colors present in their feathers. As a result, habitat quality can have lifetime fitness consequences through the color pathway. Widescale habitat change has affected the quality of habitats accessible to birds worldwide. Consequently, the availability of pigment-containing resources within many altered habitats has shifted, leading to modification in the coloration of some birds’ feathers. I hypothesized that the red pigmentation in the feather shoulders, or epaulets, of red-winged blackbirds (Agelaius …

Beyond Capture: Development And Validation Of A Method To Assess Body Condition In Mule Deer (Odocoileus Hemionus) Using Camera Traps, Rachel A. Smiley 6820420

University Scholar Projects

Advances in technology and availability associated with camera traps have resulted in a rapid rise in their use to monitor wildlife distribution, abundance, and behavior. We focus on assessing body condition, a new application of camera traps. Body condition indices must relate to the percent body fat if they are to be useful. To acquire measurements of body fat, most body condition indices require capture or mortality of animals to estimate, which has limitations when applied to free-ranging animals. We developed a non-invasive, visual body condition index (VBCI) to assess body condition of mule deer that can be applied …