CSS Archives - The Graduate School’s Student Success program

9:00-9:20	Breannah Keys Presentation Time: 9:00-9:20 Home University: UNC-Chapel Hill Research Mentor: Dorothy Erie, Chemistry Program: CSS Research Title: DNA Mismatch Repair Proteins DNA mismatch repair is essential for maintenance of genome stability. Mismatch repair (MMR) corrects errors made during DNA replication, including mismatches and insertion-deletion loops. This process enhances DNA replication by about 100 to 1000-fold by improving the accuracy of the incorporated base pairs. We used the MMR protein MutS from Thermus aquaticus as our model. Previous studies have shown that a glutamate in the DNA binding domain of MutS hydrogen bonds with a mismatched nucleotide leading to a change of shape in the DNA, determinant of repair. In this study, we were specifically interested in MutS’s interaction with thymine inserts (T-bulges) and GT mismatches. Previous studies have shown that wild type MutS can repair T-bulges and GT mismatches whereas mutating glutamate to alanine, MutS can only repair T-bulges and not GT mismatches. We have mutated the glutamate to alanine to inhibit MutS causing conformational changes in the DNA with GT mismatches leading to MMR so we could study how MutS is interacting with the DNA. To visualize the protein-DNA interaction, a Cys mutation was also introduced into the MutS protein so it could be fluorescently labeled. Single molecule fluorescence resonance energy transfer (smFRET) experiments were performed to visualize measure conformational changes of the mutated protein and DNA. FRET is a function of the distance between the donor and acceptor fluorescent dyes.	DNA Mismatch Repair Proteins	CSS
9:25-9:45	Autumn Tucker Presentation Time: 9:25-9:45 Home University: UNC-Chapel Hill Research Mentor: Dr. Leon Coleman, Pharmacology Program: CSF, CSS Research Title: Persistent Effects of Alcohol Use on Alzheimer's Disease Tau Pathology Several epidemiological studies have found that heavy alcohol use may increase the risk of developing Alzheimer’s disease (AD), although the mechanisms behind this link are unclear. The increase in neuroinflammation seen during alcohol abuse and AD may drive this connection, however, the effects of heavy alcohol use on Alzheimer’s pathology during abstinence have not been explored. Additionally, the persistent effects of alcohol abuse on the sexual dimorphism of AD pathology remain to be explored. Triple transgenic AD mice models were treated with ethanol for three months during adulthood followed by five months of abstinence to model sustained recovery following heavy alcohol use until Alzheimer’s pathology begins to develop. By visualizing brain tissue via immunohistochemistry and analyzing cortical and hippocampal protein and gene expression through western blotting and RT-PCR, the sustained changes in AD pathology as a result of alcohol abuse were studied. The two pathological hallmarks of Alzheimer’s disease (amyloid plaques and tau tangles) were measured to directly analyze these conditions. Although there was not a persistent increase in amyloid plaques as a result of alcohol use, there was a persistent increase in phosphorylated tau in female subjects, particularly in the piriform cortex, which is known to be sensitive to alcohol. There is a correlation between the increase in phosphorylated tau with long-term changes in several genes known to play a role in immunoinflammatory responses.	Persistent Effects of Alcohol Use on Alzheimer's Disease Tau Pathology	CSF, CSS
10:40-11:00	Jasmine Akoto Presentation Time: 10:40-11:00 Home University: UNC-Chapel Hill Research Mentor: Patrick Sullivan, Psychiatry Program: CSS Research Title: Assessing Transcriptional and Epigenetic Impacts of Antipsychotics Schizophrenia is a severe mental disorder that affects ~1% of the population. It is typically diagnosed during adolescence or early adulthood, and characterized by the presence of hallucinations, delusions, and grossly disorganized behavior. Antipsychotics are the primary treatment of these symptoms. Unfortunately, due to side effects, and/or lack of efficacy, about 75% of patients discontinue the use of antipsychotics. This study uses functional genomics approaches to gain mechanistic insight into the transcriptional and epigenetic changes brought about by chronic antipsychotic exposure. We carried out a dosage study (pilot study) using drug-containing chow, to determine the appropriate dose needed to achieve human-like plasma drug levels of commonly used antipsychotics. The study consisted of 8-week old male C57BL/6 mice that were randomized across 3 different treatment groups: haloperidol (1 mg/kg; 3 mg/kg; 5 mg/kg), olanzapine, and placebo (n=4 mice per treatment group). Mice were fed drug-containing chow for a period of 28 days; plasma was collected at 21 days. Body weight was recorded before and after treatment. Haloperidol treatment groups 3 mg/kg and 5 mg/kg were discontinued due to weight loss. After 28 days, mice went through cardiac perfusion, and brain regions were dissected and stored at -80°C. Dosage studies will be followed with larger groups of mice and additional antipsychotics, in order to elucidate the effects of chronic antipsychotic treatment on chromatin structure and gene expression.	Assessing Transcriptional and Epigenetic Impacts of Antipsychotics	CSS
11:05-11:25	Madyson Barber Presentation Time: 11:05-11:25 Home University: UNC-Chapel Hill Research Mentor: Andrew Mann, Physics and Astronomy Program: CSS Research Title: The Characterization of a Young Exoplanet From the Kepler Mission Due to various natural processes, planets will change over their lifetime. We can see this in our Solar System, as Mars and Venus show evidence of once liquid water, and Earth shows an evolving atmosphere and terrain. Since their initial discovery in 1992, nearly 4400 exoplanets, residing outside of our Solar System, have been confirmed. However, less than 1% are considered young planets less than 500 million-years-old. Young planet discovery aids in understanding planetary evolution. When comparing younger and older exoplanets, more data will help to create statistically significant results, thus mitigating the effects of outliers. We seek to characterize a known young planet candidate initially considered a false positive. Using neighboring stars’ properties, including kinematics, rotation, color, magnitude, and Lithium abundance, we estimate the stellar association, and thus the host star, to be 80 million-years-old. The planet is orbiting a young analog of our older Sun (5 billion-years-old) in an association overlapping with the Kepler-prime field. By analyzing the light curve, or the star’s observed brightness over time, using a Markov Chain Monte–Carlo based modeling approach taking into account our updated stellar parameters, we estimate the planet to be about twice the size of Earth (1.95±0.10R⊕) on a close-in orbit (19.58 days). Given its age and parameters, this system is valuable for the continual research on the evolution of young systems.	The Characterization of a Young Exoplanet From the Kepler Mission	CSS
11:30-11:50	Ashleigh Henry Presentation Time: 11:30-11:50 Home University: UNC-Chapel Hill Research Mentor: Dr. Rebecca Fry, Department of Environmental Sciences and Engineering Program: CSS Research Title: Epigenetic Impact of PFOS on JEG-3 Placental Cells via ATAC Sequencing and RNA Sequencing Analyses Environmental chemicals amount to a large portion of the exposures an individual experiences over their lifetime. Exposure to per- and poly- fluoroalkyl substances (PFAS) have been shown to negatively affect the health of vulnerable populations such as pregnant women and the developing fetus. Recently, perfluorooctane sulfonic acid (PFOS) in particular has become a major chemical of interest due to its ubiquity and persistence in the environment due to its chemical stability. PFOS is especially of concern in North Carolina, as samples 14 times greater than the U.S. Environmental Protection Agency’s health advisory have been found in sewage treatment plants. Exposure to PFOS and other per fluorinated chemicals are associated with adverse health outcomes, such a low infant birth weight, and pre-eclampsia. The goal of my study is to understand the impact of PFOS exposure on JEG-3 choriocarcinoma cells through ATAC sequencing and RNA sequencing analyses, which use a high through-put sequencing approach to identify open areas of chromatin and gene expression, respectively. More specifically, we aim to investigate the impact of per fluorinated chemicals on the epigenome through changes in chromatin structure. Ultimately, the genomic differences between the open chromatic regions of the exposed and unexposed cell populations could help inform the association between prenatal PFOS exposure and the relating negative health outcomes.	Epigenetic Impact of PFOS on JEG-3 Placental Cells via ATAC Sequencing and RNA Sequencing Analyses	CSS
12:20-12:40	Terrique Morris Presentation Time: 12:20-12:40 Home University: UNC-Chapel Hill Research Mentor: Jon Abramowitz, Psychology Program: CSS Research Title: Parental Needs: Psychological distress and treatment preferences among parents amidst the COVID-19 pandemic The COVID-19 pandemic has served as a major stressor, impacting millions of individuals across the world. It is likely the stress of the pandemic has had a uniquely strong impact on parents. Over the last year, substantial research has emerged on parental distress and psychological functioning amidst COVID-19. The present literature review aimed to summarize findings regarding the prevalence and severity of psychological symptoms during the pandemic, as well as its impacts on parental functioning (e.g., parenting and child outcomes). A literature search was conducted, and findings synthesized across empirical papers. Overall, findings suggest higher rates of psychological distress, such as depression and anxiety, following the pandemic. Studies have shown that increased psychological distress at this time is associated with increased distress in parent-child relationships, domestic violence, child neglect and maltreatment, and adverse parenting outcomes. This review highlights the significant psychological impact of the pandemic on parents, and how increased distress is likely to have critical impacts on parent-child outcomes. Our findings suggest further study on widespread family support and intervention is essential to decreasing the burden among parents and potential long-term individual mental health and familial relationship issues as the pandemic continues. Prioritizing the treatment of psychological disorders among parents is also of great importance to mitigate the global impact of the pandemic.	Parental Needs: Psychological distress and treatment preferences among parents amidst the COVID-19 pandemic	CSS
1:30-1:50	Carla Escobar-Tomlienovich Presentation Time: 1:30-1:50 Home University: UNC-Chapel Hill Research Mentor: Jason Stein, Department of Genetics Program: CSS Research Title: Segmentor: Training a Machine Learning Algorithm to Optimize the Accuracy of Automatic Brain Segmentation Individuals with autism often have increased head size, or macrocephaly. Previous studies have described periods of premature heightened brain development that are typically followed by stunts in development to be indicative of neuropsychiatric disorders. A novel and more accurate process of diagnosing macrocephaly includes counting the number of nuclei present in the brain by looking at imaging. However, it is currently unfeasible to count all of the neuron’s in a human’s brain; each person has about ~86 billion neurons, showing that it would manually take one individual 430 billion minutes to complete the segmentation. The Segmentor project involves the development of an annotation tool that will automate cell segmentation from 3D brain images to count how many nuclei are present. Currently, the goal of Segmentor is to create an open-source tool so that people can manually trace the brain images and feed the algorithm “good data.” This data will be used to train a deep learning process that will teach the program how to accurately evaluate where nuclei are without needing any additional human input. Therefore, the development and eventual use of Segmentor shows both improvement in how technology can be used for research and also for medical treatment itself. This program will be able to help improve brain segmentation techniques, which could eventually also be applied to various other parts of the body.	Segmentor: Training a Machine Learning Algorithm to Optimize the Accuracy of Automatic Brain Segmentation	CSS

SUP Program: CSS