The Effects of Novel Anti-Inflammatory Drugs on LPS-Induced Cytokine Gene Expression in BV2 Cells

Type: Undergraduate
Author(s): Ana Herget Biology Giridhar Akkaraju Biology
Advisor(s): Giridhar Akkaraju Biology
Location: Basement, Table 7, Position 3, 1:45-3:45

Alzheimer’s Disease (AD), the most common form of dementia, currently impacts almost seven million people in the United States over the age of 65. It is predicted that by 2060 over 13 million people in the United States will be affected by AD, which is why there is a growing demand for treatments. Amyloid ꞵ plaques and phosphorylated tau proteins are both associated with the progression of the AD pathology since they play a role in the disruption of neuronal integrity. These aggregated proteins along with other molecules, such as lipopolysaccharide (LPS), lead to increased inflammation by activating the NFκB pathway. The NFκB pathway controls the production of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFɑ); however, if it is overactive, it can lead to harmful inflammation.The company P2D Biosciences provides novel compounds designed to reduce inflammation, but the exact mode of action of these compounds is unknown. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) can be utilized to measure cytokine mRNA from BV2 cells that have been pretreated with the drugs and then with LPS. In this project we screened multiple compounds provided by P2D Biosciences to evaluate their use as anti-inflammatory agents to treat AD.

Investigating the ubiquitin ligase activity of BRCA1 from C. elegans

Type: Undergraduate
Author(s): Lauren Herrington Biology
Advisor(s): Mikaela Stewart Biology
Location: Third Floor, Table 8, Position 1, 1:45-3:45

BRCA1 is a tumor suppressor protein that normally acts with its partner, BARD1, to facilitate DNA repair, regulation of the cell cycle, and regulation of gene expression. The Caenorhabditis elegans homologs of BRCA1 and BARD1, BRC-1 and BRD-1, respectively, retain these key functions and thus make C. elegans a suitable model organism for studying the functions of BRCA1. While the functions of BRCA1 and BRC-1 are well characterized, the molecular mechanisms by which these functions are carried out is still unclear. For example, BRCA1 and BRC-1 possess E3 ubiquitin ligase activity towards histone H2A in nucleosomes, but it is unknown how this contributes to tumor suppression. While inherited mutations that disrupt tumor suppression lack E3 ligase activity, they also interfere with other critical molecular functions, such as BARD1 binding. To pinpoint the role of E3 ligase activity, we aim to characterize a mutant construct of BRC-1 in C. elegans that lacks E3 ubiquitin ligase activity towards histone H2A but retains the ability to bind BRD-1. In vitro ubiquitination assays demonstrate that our candidate for this mutant of BRC-1, Trip A, is ligase-dead towards histone H2A in nucleosomes. Co-purification of BRC-1 and BRD-1 in which only BRC-1 contained the histidine tag revealed that BRC-1:BRD-1 binding is retained in the Trip A mutant. While these results demonstrate that Trip A meets in vitro requirements for a ligase-dead mutant, further in vivo experiments are needed to confirm its suitability. If confirmed as a suitable ligase-dead mutant through in vivo experiments, Trip A can be expressed in C. elegans to identify which functions of BRC-1 depend on E3 ubiquitin ligase activity towards histone H2A in nucleosomes.

Identifying the nucleosome ubiquitylation role of BRCA1 in transcriptional regulation using C. elegans

Type: Undergraduate
Author(s): Elizabeth Hoff Biology
Advisor(s): Mikaela Stewart Biology
Location: FirstFloor, Table 1, Position 1, 1:45-3:45

BRCA1 is a tumor suppressor protein that facilitates DNA damage repair, cell cycle checkpoints, and gene expression in humans. The presence of pathogenic mutations in the BRCA1 protein leads to a predisposition to breast and ovarian cancers in humans; these pathogenic mutations can lead to the dysregulation of enzymatic activity and gene expression. It is hypothesized that enzymatic activity of BRCA1 and its ability to regulate gene expression are linked. The gene expression of estrogen-metabolism genes by BRCA1 is mediated, in-part, by the ability of BRCA1 to facilitate the mono-ubiquitylation of nucleosomes on the H2A histone. Our lab is interested in understanding which DNA damage repair and gene expression functions of BRCA1 rely on mononucleosome ubiquitylation. In Caenorhabditis elegans, the BRCA1 homolog, BRC-1, retains the key functions of BRCA1, making C. elegans a suitable model organism to evaluate which functions of BRCA1 rely on nucleosome ubiquitylation. To explore nucleosome ubiquitylation by BRC-1 in C. elegans, we compare three strains of C. elegans, including a wildtype strain, a complete knockout of BRC-1, and an engineered mutant. This engineered mutant contains two point mutations that alter the ability of BRC-1 to interact with the nucleosome to complete ubiquitylation of the H2A histone. We suggest that our proposed mutant repels BRC-1 from the histone to prevent ubiquitylation, yet retains all other BRC-1 functions. We hypothesize that this will hinder the repression of cyp genes, which code for enzymes that catalyze the process that converts estrogen into various metabolites, some of which are harmful. Overexpression of these genes can lead to the accumulation of harmful estrogen metabolites, which can lead to tumorigenesis in estrogen-metabolizing tissues. To assess this, we compare the expression levels of cyp genes, which are repressed in the wildtype strain containing a functional copy of BRC-1. If mononucleosome ubiquitylation is required for transcriptional repression in C. elegans, in the engineered mutant strain, we expect to see elevated levels of cyp gene expression, as also seen in the complete BRC-1 knockout strain. Through understanding the mono-ubiquitylation of nucleosomes by BRC-1 in C. elegans, we can better interpret the genetic variations of BRCA1 in humans and better inform and treat patients with detrimental BRCA1 mutations.

Trade-offs between environmental concerns and disease control influence disease dynamics across communities

Type: Undergraduate
Author(s): Redon Limani Biology Kenny Lai Biology Grant Xiong Biology
Advisor(s): Jing Jiao Biology
Location: Third Floor, Table 6, Position 2, 11:30-1:30

Mosquitoes are primary vectors in the transmission of many infectious diseases, spreading pathogens through their bites after feeding on infected
hosts. Vector-borne diseases like Zika, chikungunya, and yellow fever, mostly transmitted by mosquitoes, cause over 700,000 deaths each year and
account for 17% of infectious diseases, heavily burdening vulnerable communities and economies. Public perception of mosquito control can significantly shape outbreak outcomes [1]. This project uses a mathematical model to simulate how disease spreads between two regions connected by mosquito migration. The model considers how people’s concern for the environment can influence their support or opposition to mosquito control efforts. Our goal is to explore how these factors shape disease prevalence and to better understand the role of community behavior in outbreak prevention.

New Smiles Drive

Type: Undergraduate
Author(s): Alexandra Much Biology Aimee Garibay Interdisciplinary Annie Loomis Biology Sarina Schwarze Biology Kameryn Smudde Nutritional Sciences
Advisor(s): Sarah Jung Biology
Location: SecondFloor, Table 8, Position 2, 11:30-1:30

Oral health is a critical component of overall well-being, yet many individuals in underserved communities lack access to essential dental care and hygiene resources. The New Smiles Drive is a student-led initiative dedicated to improving oral health education and access to hygiene supplies in the Fort Worth community. Through the TCU Tooth Fairies program, we present at elementary schools, engaging students in interactive lessons on proper brushing and flossing techniques to foster lifelong oral hygiene habits. Additionally, we donate hygiene kits—containing toothbrushes, toothpaste, floss, and a laminated educational card outlining proper brushing steps in both English and Spanish—to Mercy Clinic, which provides medical and dental care to uninsured patients, as well as to local homeless shelters. By combining education with tangible resources, New Smiles Drive aims to promote preventive dental care and address disparities in oral health access.

In Vitro Evaluation between 5-LO Inhibitor, Zileuton, and Antifungal Activity Against Cryptococcus

Type: Undergraduate
Author(s): Khoi Nguyen Biology Natalia Castro Lopez Biology Floyd Wormley Biology
Advisor(s): Natalia Castro Lopez Biology Floyd Wormley Biology

Total Mercury (THg) Levels in Tricolored Bats (Pipistrellus subflavus) in East Central Texas

Type: Undergraduate
Author(s): David Peebles Biology Cami Middlebrooks Biology Benjamin Strang Biology
Advisor(s): Matt Chumchal Biology
Location: SecondFloor, Table 3, Position 3, 11:30-1:30

Mercury (Hg) is a trace element metal with toxic effects on wildlife, including bats. Texas is the largest producer of mercury pollution in the United States, yet only 2 other studies have measured the concentration of mercury in bats. We measured total mercury concentrations (THg) in fur (n=57) in the endangered species Tricolored bats (Pipistrellus subflavus) collected from two culverts in Fresstone County in East Central Texas. Fur THg concentrations were compared between sex, culverts, and previous studies in the U.S.. There was no significant difference in THg between sex or culvert, but there was a significant difference with the Tricolored bats in the Northeastern U.S.. However, the THg values were not significantly different from those of previous studies conducted in Texas. Additionally, the THg concentrations were compared with the 10 ug/g toxicity threshold levels commonly used, with 5.2% of Tricolored bats in this study exceeding this toxicity threshold. This suggests that THg may pose a risk to the health of bats in East Central Texas, and protective measures need to be implemented to protect this species.

Examining oxidative stress models in mouse neuron HT-22 cells to explore neuroprotective features of antioxidant compounds.

Type: Undergraduate
Author(s): Caleb Pryor Biology Michael Chumley Biology Raleigh Robinson Biology
Advisor(s): Michael Chumley Biology
Location: SecondFloor, Table 3, Position 2, 11:30-1:30

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that affects millions worldwide and has shown increasing prevalence. The pathological hallmarks of AD include amyloid-beta (Aβ), tau hyperphosphorylation, and neuroinflammation. It has become increasingly apparent that oxidative stress from reactive oxygen species (ROS) accumulation plays a crucial role in AD disease progression. ROS contributes to neuronal dysfunction and death by inducing lipid peroxidation, mitochondrial impairment, and chronic inflammation. We utilized the HT-22 mouse neuronal cell line to investigate oxidative stress and potential neuroprotection in vitro following glutamate induced oxidative stress. To assess oxidative damage and neuron death, we utilize the MTT assay to measure cell viability following glutamate treatment. Novel antioxidant compounds synthesized from Dr. Green’s labs have been shown to be radical scavengers and increase expression of antioxidant pathways. We additionally pre-treated HT-22 cells with these novel antioxidant compounds prior to glutamate exposure to evaluate their effectiveness in scavenging ROS and preventing oxidative damage. Results from these experiments will lay the foundation for further testing to determine the mechanism in which these novel antioxidants show neuroprotective effects, which could provide valuable insight into antioxidant based therapeutic strategies for AD and other neurogenerative diseases.

Influence of LPS-Treated BV2 Supernatants on Glutamate-Induced Ferroptosis in HT22 Cells

Type: Undergraduate
Author(s): Raleigh Robinson Biology Caleb Pryor Biology
Advisor(s): Michael Chumley Biology Gary Boehm Psychology
Location: FirstFloor, Table 1, Position 2, 11:30-1:30

Alzheimer’s disease (AD) was the fifth leading cause of death in people over 65 in 2021, and it is expected that 13 million Americans will have AD by 2050. AD is a neurodegenerative disease that is characterized clinically by the onset of memory loss and cognition decline in aging populations. These clinical manifestations of AD are a result of neuronal cell death. While our knowledge of the exact pathology of AD is still evolving, inflammation of the central nervous is known to be a factor in the onset and progression of AD. Microglial cells are one major cell type responsible for this inflammation. Microglial overactivation, which leads to the overproduction of proinflammatory cytokines, is thought to be a cause of the chronic inflammation seen in AD. Additionally, ferroptosis, which is a regulated form of cell death characterized by iron-dependent lipid peroxidation, is thought to be a major mechanism by which neurodegeneration occurs in AD. HT22, an immortalized cell line of mouse hippocampal neurons, are a commonly used model for studying ferroptosis. Furthermore, BV2 cells are an immortalized cell line of mouse microglial cells that produce inflammatory cytokines that can be removed in their “conditioned” media. We treated HT22 cells with glutamate to induce ferroptosis, and also with BV2-conditioned media, and measured the cell death via an MTT assay to investigate whether the proinflammatory cytokines produced by microglial cells also induces the neuronal cell death that occurs via ferroptosis. These studies are ongoing.

SEX RATIOS OF SILVER-HAIRED BAT (LASIONYCTERIS NOCTIVAGANS)​ FATALITIES AT WIND ENERGY FACILITIES IN SOUTHERN INDIANA​

Type: Undergraduate
Author(s): Gabby Ross Biology
Advisor(s): Dr. Dean Williams Biology
Location: Third Floor, Table 3, Position 1, 1:45-3:45

Wind energy is considered one of the fastest growing renewable energy sources. However, bat collision mortality has become an increasing issue for migratory bat species over the years. Researchers are interested in a sex bias in the mortality rates at wind farms. If females are being disproportionately killed, the population will not sustain itself over time and their numbers will decrease. The goal of my study was to determine the sex ratio of silver-haired bats killed at a wind farm and determine if females are experiencing higher mortality than males. These data allow scientists to implement curtailment that reduces collision fatalities. Curtailment is the turning off of wind turbines on low wind speed nights, the nights where bat mortalities are highest. Researchers can also use the information to target curtailment when females are at their highest risk for collisions. I extracted DNA from 66 bat samples originating from a wind farm in Southern Indiana. To determine the species for a subset of the samples I sequenced a portion of the mitochondrial cytochrome oxidase I gene which is the DNA barcode region that can be used to identify species, I then used X and Y genetic markers to determine the sex of all samples. Of the 66 samples, 9 were spot checked for species identification via sequencing and were identified as silver-haired bats. Out of the 66 samples, 29 (43%) samples were identified as female and 37 (66%) were identified as male. This ratio did not differ from a 50:50 sex ratio (x2=0.97, p = 0.32). We can conclude that our sample set has a 50:50 sex ratio of males to females for silver haired bats. We compared our data to previous studies on silver haired bats and noticed a similar pattern for several other states in the US. The only state to have a statistically significant difference in their sex ratio of females to males was Ohio, which had a sex ratio of 2.1 females for every male. Since the results indicate a 50:50 sex ratio, curtailment during migration periods could be equally effective for both sexes to maintain the population of silver haired bats over time. Further research also indicates that acoustic deterrence is an unequivocally effective method for deterring bats from wind turbines.