Summer 2023

Levi Raskin

Advisor: Maja Šešelj

Is Dental Development an Honest Signal of Phylogenetic Placement?

The scarcity of data usable for interpreting the human evolutionary past has forced paleoanthropologists to utilize characteristics in phylogenetic analysis without the requisite study required to understand whether those traits are in fact phylogenetically informative. Dental development, like many characteristics related to life history, is highly variable between taxa and while there may be clear trends at higher taxonomic rankings, the variability of life history traits beguile classification at lower taxonomic levels, like tribe. Despite that, because of the abundance of teeth in the fossil record, dental traits have been utilized to resolve hominin phylogenies almost since its methodological inception. In particular, easy-to-access characteristics like perikymata, a roughly weekly growth line visible on the tooth’s surface, have been used recently to try and resolve speciation in situations where either hominin phylogenetics are poorly understood or there is a paucity of skeletal evidence.

By continuing the reaction against dental development in phylogenetics begun by Kufeldt and Wood (2022), we will expand on their conclusions and disseminate to the paleoanthropological community how, where, and in what ways perikymata can, or cannot, be used in phylogenetics. This summer, we are imaging casts of great gpe teeth to collect data on perikymata counts to eventually test their ability to resolve evolutionary relationships in the great ape clade. If perikymata cannot reproduce the known phylogeny within the great apes, then we will have to doubt its power for reconstructing evolutionary relationships within hominins. If perikymata are able to clearly recreate the genetic tree, then perikymata may be a true proxy of evolutionary relatedness. While more studies at lower taxonomic levels should be conducted, its usage in paleoanthropology would tentatively be supported.

Kyle Bledsoe

Advisor: Adam Williamson

CRISPR-Cas9 edited cell line library to understand the fundamental biology of Batten Disease

Batten Disease is a set of pediatric, neurodegenerative lysosomal storage diseases caused by mutations in any of fourteen different CLN genes. Even though all but one of the genes have been identified, the fundamental biology underlying the role of these proteins and the disease is still not well understood. Additionally, very few models of the disease has been done in human cells. The Williamson lab focuses on the basic biology of the immune system through studying phagocytosis, an ancient method used to clear debris inside cells. Lysosomes digest the material gathered through phagocytosis, so knowing the role of these proteins in phagocytosis is critical to understanding their disease phenotypes. To understand more about the proteins and their role in phagocytosis and Batten disease, I will begin making a library of CRISPR-Cas9 edited cell lines. This library will create a way to study Batten disease and the data generated will greatly increase the knowledge about the role of CLN proteins and Batten disease itself.

Clementine Chen

Advisor: Bárbara Bitarello

Evaluating the evidence for adaptive evolution of the TAS2R38 bitter taste receptor gene in primates

Background: As one of the senses that enable people to discern and differentiate diverse flavors, taste is facilitated by taste receptors. There are two types of taste receptors, with type I in charge of detecting salty tastes and type II receptors detecting sweet, umami, and bitter tastes. TAS2R, the gene family encoding type II taste receptors, specifically account for bitter taste receptor function. These receptors are characterized as G-protein coupled receptors (GPCRs). Within this protein family, 25 protein-coding genes and 11 pseudogenes are present in humans. Collectively, they are capable of interacting with a vast array of molecules, each receptor exhibiting unique molecular affinities.

Due to the fact that bitterness is important for animals to potentially prevent swallowing poisonous substances, we believe that the TAS2R genes that code for bitter taste receptors may have evolutionary significance to humans and other primates. Especially, the gene TAS2R38, which binds to 23 known ligands, is one of the most studied among the TAS2R family. This gene is specifically associated with the perception of the taste of phenylthiocarbamide (PTC), a chemical whose structure closely resembles goitrin, a naturally occurring chemical in the cabbage family, including vegetables such as broccoli. Due to genetic polymorphisms within populations, individual perceptions of PTC's taste can greatly vary. Some scientists speculate that human ancestors' ability to perceive the taste of natural chemicals, similar to PTC, would have assisted in avoiding toxic plants, thereby suggesting the possible evolutionary significance of the TAS2R38 gene. Previous studies showed that, in humans, there are two distinct TAS2R38 haplotypes at moderate frequencies, suggesting the presence of long-term balancing selection. However, a recent study proposes that demographic events in human evolution can account for the recent evolution of this gene, thus restricting balancing selection to the distant evolutionary past of TAS2R14.

Question & Hypotheses: Due to the contradictory results from prior studies, we aim to gain clarity on whether the TAS2R38 gene underwent adaptive evolution (positive selection and/or balancing selection) in humans and other primates and, if so, under which timescales. If so, are there specific sites that show increased rates of evolution? We hypothesize that the evolutionary significance of each site is related to their ligand binding ability, and we anticipate observing an elevated dN/dS value (the ratio of nonsynonymous substitution rate to synonymous substitution rate, a measure of adaptive evolution) at sites that determine ligand specificity. We also want to test if there are any primate lineages where we find evidence for accelerated evolution for the TAS2R38 gene. In addition, another test will be conducted to determine whether TAS2R38’s evolution has been influenced by the specialized diets of humans and other primates as we hypothesize that feeding habits could play a role in shaping the genetic variations of the TAS2R38 gene.

Preliminary Findings and Continuing Work: Throughout the past year in the Bitarello Lab, we’ve been working to conduct a phylogenetic analysis of 53 primate species by creating phylogenetic trees using the aligned genes and finding the sites of TAS2R38 genes of primates and humans that are suggested to have been subjected to adaptive evolution. By using molecular evolution models in HyPhy and PAML, we confirmed by different tests that specific sites of TAS2R38 have strong evidence of positive selection. Moving forward, the branch test and branch-site test are our next steps to work on. Using the branch model, we will assess the variation in the rate of evolution (dN/dS value) across different branches in the phylogenetic tree, enabling the identification of lineages under positive selection. On the other hand, the branch-site model allows us to confirm the evidence of positive selection at individual sites along specific branches, providing a more fine-grained picture of the adaptive molecular evolution of the TAS2R38 gene.

The findings from phylogenetic analysis could offer new perspectives in various scientific domains. Understanding the evolutionary importance of the TAS2R38 bitter receptor gene enhances our comprehension of cultural evolution across human history and the impact of dietary preferences on human evolution. Additionally, identifying the sites subject to adaptive evolution aids in comprehending the mechanism of ligand binding in the bitter taste receptor or other selective pressures, hitherto unknown, that may be driving such accelerated evolution, and this knowledge can assist in the development of medications with a higher tolerance for patients.

Jessica Cramer

Advisor: Gregory Davis

Using RNAi to Knockdown Insulin-Like Peptide Signaling Pathway in the Pea Aphid (Acyrthosiphon pisum)

The Davis Lab is investigating the pea aphid, Acyrthosiphon pisum, which exhibits a reproductive polyphenism in which individuals of the same genotype develop into asexual and sexual forms depending on environmental conditions. During the summer, when days are long, aphids reproduce asexually via live birth (viviparously) but, as it gets closer to winter and the days get shorter, aphids can sense this change and give birth to offspring that develop to reproduce sexually. These offspring are both male and female, the latter of which will lay eggs (making them oviparous) that are able to withstand the winter frost. In the spring, these eggs will hatch into another round of asexually reproducing aphids. This switch in reproductive modes is thought to be mediated by an unknown biochemical factor known as “virginoparin,” which is produced by the mother and delivered to her embryonic progeny prior to birth.

Previous work in the Davis lab using the anti-insulin pathway drug wortmannin has suggested that insulin signaling may be required to specify asexual fate, with the tantalizing possibility that insulin-like peptides (ILPs) produced in the aphid’s brain may constitute virginoparin. Wortmannin, however, is capable of interfering with multiple signal transduction pathways other than the insulin pathway. A study done by Cuti et al. (2021) found that ILP1 and ILP4 are synthesized by a group of neurosecretory cells (NSCs) known as Group 1. These ILPs are potentially delivered to the embryo by the mother via the mother’s nervous system, as they are released very close to the site where the embryos are developing. We propose to test whether ILPs are required for specifying asexual fate by injecting double stranded RNA (dsRNA) against ILPs to trigger RNA interference (RNAi), a technique that has been used successfully in aphids to interfere with gene function, and block the ability of the mother aphid to deliver ILPs to her developing embryos. In order to do this, we would try both injecting dsRNA directly into aphids and delivering dsRNA via plant-mediated feeding. Both techniques have successfully been shown to transmit dsRNA and activate RNAi in aphids (e.g., Ding et al. (2017)). We  expect that with the mother aphid no longer able to transmit the ILPs to the developing embryos, they will default to the sexual fate. By blocking both the ability of the mother to send ILPs to the embryos and the ability of the embryos to receive the ILP signal, we hope to gain a clearer understanding of the possible role that ILP signaling plays in the aphid reproductive polyphenism.

Daphne Hansell

Advisor: Bárbara Bitarello

Balselr: An R Package for the Detection of Long-term Balancing Selection using the Non-central Deviation (NCD) Statistic.

Balancing selection plays a vital role in preserving genetic diversity, contributing to the adaptability and resilience of populations. Its detection is integral to understanding the evolutionary pressures and mechanisms that drive and maintain this diversity. Despite its evolutionary significance, there is a shortage of quantitative methods to measure balancing selection.

Bitarello et. al (2018) introduced a novel statistic, the Non-central Deviation (NCD), to address this issue. The NCD, in both its polymorphism-only (NCD1) and polymorphism-with-fixed-differences (NCD2) versions, offers an efficient and robust method to detect long-term balancing selection (LTBS). While scripts for these calculations were initially made available, their widespread and effective use has been limited, often due to the need for specialized knowledge and potential inaccuracies in individual implementations.

Here, we introduce balselr, a comprehensive R package designed to bridge this gap. Balselr will operationalize the NCD approach, enabling researchers to identify regions of the genome under LTBS efficiently. This will allow researchers to leverage both single-locus data and broader genomic data with an accessible, easy-to-use interface, even for individuals with basic proficiency in R. The package will not only performs calculations of NCD1 and NCD2 statistics but also facilitate the preparation of input files based on commonly used data formats in the field, such as VCF files for SNP data. The package will also provide help pages and tutorials on GitHub.  By making using the NCD statistic more accessible, balselr aims to catalyze advances in our understanding of the prevalence, targets, and broader implications of LTBS in population and evolutionary genetics.

Sam Kim

Advisor: Gregory Davis

Investigating Insulin-like Peptides as the Maternal Signal in Determining Acythosiphon pisum Reproductive Fate

Understanding the mechanism of developmental plasticity can provide insight into phenotypic evolution and the ability to adapt to one's environment. In the G. Davis Lab, the pea aphid, Acythosiphon pisum, serves as a model organism for studying developmental plasticity in that this species exhibits several cases of discrete plasticity, a phenomenon known as polyphenism. For example, in the so-called reproductive polyphenism, aphids produce asexual versus sexual progeny during cyclical parthenogenesis in response to seasonal changes in night length. Specifically, short summer nights cue the production of asexual females, which reproduce viviparously. In contrast, long fall nights cue the production of sexual females, which reproduce oviparously.

This summer, I plan to study the reproductive polyphenism of aphids and the mechanism that mediates the effect of night length on reproductive fate. Previous studies suggest that short nights cue a maternal signal that specifies the asexual fate when received by embryonic progeny. This asexual-promoting maternal signal is known as virginoparin and is the focus of my study. Two competing hypotheses suggest that virginoparin is either juvenile hormone (JH) or insulin-like peptides (ILPs), respectively. Available evidence suggests that the JH is sufficient to promote but not maternally required to specify asexual fate, while ILPs are required to specify asexual fate. If insulin is virginoparin and JH acts to up-regulate insulin, it would explain why JH is sufficient but not required to specify asexual fate. My goal this summer is to apply both JH, and Wortmannin, a drug that inhibits the insulin pathway, to aphids to potentially establish that the sufficiency of JH to specify asexual fate is in fact dependent on the insulin pathway, providing support for this model.

Gillyoung Koh

Advisor: Bárbara Bitarello

Investigation of Long-Term Adaptive Evolution In TAS2R14, A Promiscuous Bitter Taste Receptor In Primates

One of the research areas in the Bitarello lab is on the T2R or TAS2R gene family, which are genes coding for Type II taste receptors that allow organisms to taste bitterness via binding of bitter agonists to their corresponding receptor(s). We are specifically focusing on TAS2R14 (Taste receptor type 2 member 14), which is very promiscuous and binds to more than 150 known, diverse bitter agonists. This is roughly twice the second-highest number of known ligands that a bitter taste receptor from the T2R family can bind to. One study by Bitarello et al. (2018) suggested long-term balancing selection (preservation of certain alleles in a population over long periods of time) may have played a role in the evolution of TAS2R14 (the gene that codes for this receptor) in the primate lineage. 

We are testing to see whether adaptive evolution in TAS2R14 occurred and in which codons. If we see significantly high rates of nonsynonymous substitutions / synonymous substitutions (dN/dS) in codons involved in recognizing and/or binding to bitter agonists, this would suggest that adaptive evolution targeted codons involved in binding specificities of the receptor. We hypothesize that we will find codons involved in receptor-agonist interactions to undergo long-term adaptive evolution. This stems from the widespread view that being able to taste bitter compounds has an adaptive role in preventing the ingestion of toxic compounds, which are often bitter. Additionally, we want to see if phylogenetic groupings based on taxonomy or dietary preferences have undergone certain selective pressures. 

In the past year, we ran several phylogenetic tests to assess whether this gene, overall, has undergone adaptive evolution in primates and, if so, in which sites specifically. We used HyPhy, a software package that implements several codon substitution models. From HyPhy, we used GARD, BUSTED, FEL, MEME, and SLAC. GARD looks for breakpoints in the data, which are signs of recombination and can lead to false positives in the data concerning adaptive evolution. After finding no breakpoints, we used BUSTED to look for broad evidence of adaptive evolution. The BUSTED results we obtained suggested that there is evidence of adaptive evolution, without pointing to specific sites or lineages in the tree. Then, we ran FEL, MEME, and SLAC to find codon sites under adaptive evolution using a p ≤ 0.1 criterion. We discovered suggestive evidence of long-term adaptive evolution, but we want to obtain additional supporting evidence to either support or not support our hypothesis. 

Moving forward, we will use PAML, a package of programs to use for analyzing our DNA sequences, to find codon sites under adaptive evolution and compare with the found codon sites from HyPhy. We aim to find a reliable set of specific codons in TAS2R14 that have been targeted by long-term adaptive evolution by overlapping results from different models and assess whether these codons correspond to areas of the receptor that interact with the bitter agonists. We will also use branch models to assess which primate lineages specifically have been subject to this long-term adaptive evolution for TAS2R14, and whether this corresponds to different diets observed in primates. 

Angie Quiroz

Advisor: Thomas Mozdzer

Stomatal Conductance in Relation to Fluorometry in Phragmites Australis

The Mozdzer lab has been looking at Phragmites Australis, an invasive marsh species that can be used as a model organism due to their dominant and efficient growth globally. Their ecological perseverance and genetic diversity is crucial to understanding how their genetic makeup plays a role in determining favorable characteristics which can be used to modify and support coastal wetlands. There are various components and areas of focus regarding this common reed, therefore, it is critical that I get exposure to gathering different types of data from relative growth rate to light curves which I can use to connect and interpret my own project. Over the course of the summer, I will be looking at stomatal conductance and fluorescence which measures, chemical reactions and physiological aspects of the plant by using the Li-600 Promoter/Fluorometer. I hypothesize that plants with greater nocturnal stomatal conductance are susceptible to a greater rate of withering. This will give us more insight to how plants with a different genetic makeup may respond to future levels of elevated carbon dioxide. Given that Phragmites Australis is an invasive marsh species, there have been countless efforts to remove it from coastal wetlands, however, these experiments could shine light on previous studies that also hint at the benefits of this common reed. The money that goes towards eliminating Phragmites Australis could instead be used for more experiments to determine ways in which the presence of invasive marsh species could become more beneficial to surviving the effects of climate change on coastal wetlands. 

Gwendolyn Rewoldt

Advisor: Thomas Mozdzer

Investigating heritable trait variation in functional model plant Phragmites australis

My project is part of the bigger C-EVO project which is investigating how rapid evolution in response to global changing factors and ecological processes are potentially interacting and influencing each other using salt marsh Phragmites australis as the study organism. Salt marshes are a very productive ecosystem with a limited number of species and many ecosystem engineers, like Phragmites. While results from prior studies indicate that Phragmites traits related to C cycling exhibit heritable variation, my current project is gathering data on traits and their variation between the 198 unique genotypes with a focus on leaf canopy traits to further assess heritable versus non-heritable traits. Here at Bryn Mawr, we are conducting a huge common garden experiment where we have taken 198 individuals with unique genotypes to assess if measures of individual plant traits are correlated with C cycling and if they are heritable. Using methods like collecting SLA samples, measuring stem heights, and potentially measuring leaf thickness, my measurements will be used to parameterize a model to further evaluate the potential influence of evolution on C cycling. I hypothesize that we will see different measurements of leaf canopy traits that are correlated with genotypic variation. In the following years, the project will continue by crossing each dam with a different sire, creating a F1 generation with known parentage from which functional trait data can be collected to estimate heritability.    

Shriya Sai Shivakumar

Advisor: Bárbara Bitarello

Assessing the impact of smoking behavior on genetic blood trait variation via alcohol intake through multi-ancestry analysis

Genome wide association studies (GWAS) have associated thousands of loci with quantitative human blood trait variation. Blood trait loci and related genes may regulate blood cell-intrinsic biological processes, or alternatively impact blood cell development and function via systemic factors and disease processes. Observational studies show conflicting results. Studies have shown that both alcohol and smoking behaviors impact blood cell traits. Smoking was linked with higher red blood cell and hemoglobin count, and alcohol showed altered blood cell traits and function. Clinical observations linking behaviors like tobacco or alcohol use with altered blood traits can be subject to bias, and these trait relationships have not been systematically explored at the genetic level. They could be subjected to unmeasured or unrecognized confounding factors. Previous blood traits GWAS adjusted for both tobacco and alcohol use behaviors based on presumed multi-trait impacts (instead of specifically blood traits) but the effects of these behaviors on specific blood traits or developmental lineages are unclear. The Vuckovic et al Cell 2020 GWAS was not adjusted for smoking or alcohol use, and has increased power, giving the opportunity to analyze the determined effects of these behaviors on blood traits.

Using a Mendelian randomization (MR) framework using GWAS summary statistics, we can confirm causal effects of smoking and drinking on different blood lineages. Using Multivariable MR (MVMR) and causal mediation analyses, we can identify mediating or confounding traits to explain the causal effect. MVMR can also help establish a causal direction between smoking and alcohol as they are highly genetically correlated. We previously did this for GWAS from entirely European cohorts (Shivakumar et al. 2023) and showed that there is a casual direction from Smoking to Drinking, and that drinking has a significant negative effect on erythroid traits. After correcting for the exposure of alcohol, we negated all the significant effects of tobacco use on blood cell traits.

However, the majority of GWAS and overall collected samples/data are based on a white European ancestry, leading to a dangerous lack of representation in the studies and associations.This has been shown to impact the utility of tools like polygenic risk scores and CRISPR editing in groups not represented in the original studies, so diversifying studies is critically important.  Moving forward, we will replicate our analyses in a multi-ancestry approach. Using the filtered meta-analysis summary statistics and polygenic risk score from the Saunders multi-ancestry meta analysis of 3.4 individuals, we will analyze ​​nicotine and substance use and check for disparities among different GWAS. We hope to confirm that what we observed in Europeans is true for other groups as well. Collectively, our findings might demonstrate a novel role for genetically influenced behaviors in determining human blood traits, revealing opportunities to dissect related pathways and mechanisms that influence hematopoiesis.

Jo Smith

Advisor: Thomas Mozdzer

Heritable trait variation in relative growth rates and herbivory among Phragmites australis genotypes from two populations

Salt marsh ecosystems provide many vital ecosystem services, but their existence is threatened by accelerating global change factors including rising concentrations of CO2, nutrient pollution, and human development. The common reed, Phragmites australis, is considered to be a new model organism for both invasive species and plant physiology. Recent research has demonstrated that exposure to both near future levels of CO2 and nutrient enrichment have reduced intraspecific levels of genetic diversity and altered plant traits suggesting that populations are rapidly evolving. In order to evaluate the heritability of plant traits, 120 unique genotypes of P. australis were collected from two populations in MD, USA, the Smithsonian Global Research Wetland (Edgewater, MD) as well as Parker’s Creek (Prince Frederick, MD). A total of 240 genotypes were grown in a common garden at Bryn Mawr College.The common garden allows me to evaluate heritable traits by removing confounding environmental factors. Given previous research that shows plants exposed to elevated nitrogen have an increased relative growth rate as well as a higher number of aphids per plant. These findings hypothesize that genotypes that were treated by nitrogen will have a higher growth rate and aphid density than plants that were not exposed to elevated nitrogen. I measured plant relative growth rate by measuring the height of 3 tagged shoots from each pot. In addition, given evidence of differential herbivory, also measured the presence and severity of different types of herbivory between the plants. Herbivory was categorized between sucking insects such as aphids, chewing insects and animals, and stem boring insects. This research aims to provide insights into which traits are heritable, to provide further insight to the evolutionary ecology of salt marshes as a whole.

Chloe Tang

Advisor: Tamara Davis

Methylation patterns of multiple DMRs in 12.5 dpc wild type and methyltransferase mutant mouse embryos

Mammals have evolved to have many forms of gene regulation and genomic imprinting is one of the forms that only allows the expression of one parental allele from an organism’s genome. Imprinted genes are regulated epigenetically through DNA methylation, facilitated by DNA methyltransferase (Dnmt1), where a methyl group (CH3) is added to one allele to generate a differentially methylated region (DMR). The methylated allele is silenced, leading to differential gene expression of the parental alleles. Methylation at primary DMRs, which is inherited at fertilization, is stable and symmetrical across development whereas methylation at secondary DMRs, which is acquired during early embryogenesis, is less stable and asymmetric. The proper establishment of methylation patterns is crucial for embryonic development as abnormal  methylation patterns can lead to inappropriate gene expression, developmental disorders and diseases such as cancer.

In addition to different methylation patterns between primary and secondary DMRs, previous research suggested that methylation is well maintained at primary DMRs in mouse embryos with a hypomorphic mutation of Dnmt1 (p allele) but is dramatically reduced at secondary DMRs. These pieces of evidence implied that Dnmt1 might function differently at different loci. We noticed that secondary DMRs have greatly reduced methylation in P allele mice and wanted to understand the reason behind this. We hypothesize that the increased hemimethylation levels are due to reduced Dnmt1 fidelity. To understand the underlying mechanism of this methylation loss, I am analyzing the methylation patterns at multiple primary and secondary DMRs in 12.5 days post conception (dpc) wild-type and Dnmt1 mutant mouse embryos to test this hypothesis.

Juanita Beenyi

Advisor: Yan Kung

Kinetic and structural characterization of an archaeal mevalonate kinase

The mevalonate pathway, also known as the HMG-CoA reductase pathway, is a metabolic pathway that plays a crucial role in the biosynthesis of steroids such as cholesterol and isoprenoid natural products. The pathway consists of seven different enzymes responsible for synthesizing the precursors to steroids and isoprenoids. One enzyme, mevalonate kinase, catalyzes the first of three consecutive reactions that use ATP. In addition, downstream products of the mevalonate pathway can cause feedback inhibition of mevalonate kinase, but this varies among different organisms. In some archaea, however, MK activity has been found to be unaffected by all downstream products known to cause feedback inhibition. Could MK in archaea be resistant to feedback inhibition? To address this question, I will study the kinetics and structure of MK from Methanocaldococcus jannaschii (MjMK). I will express and purify MjMK and characterize its kinetics to study its activity and possible inhibition. I will also determine its three-dimensional structure by protein X-ray crystallography. The results of this experiment will lead to a better understanding of the structure of MK and how its structure governs its activity and regulation.

Cameron Blair

Advisor: Ashlee Plummer-Medeiros

Purification of YebS Using Different Detergents to Assess Protein Yield

YebS/T is a lipid transport membrane complex found in E. coli and other gram-negative bacteria. These bacteria are composed of a double lipid bilayer, consisting of the inner membrane and the outer membrane, which are separated by the aqueous periplasm. YebS is a transmembrane protein found in the inner membrane, which is thought to be responsible for handing off lipids to YebT in the periplasm, for the purpose of moving lipids from the inner to the outer membrane. This enables cell growth and creates membrane stability. Studying this complex’s structure and function will improve understanding of bacterial membrane stability, which will aid in the development of antibiotics, as bacteria cannot survive when their membranes are unstable or unable to expand. This research aims to express and purify E. coli YebS under varying detergent conditions to test which will yield the largest amount of purified protein. This is important as detergents are useful in solubilizing proteins as their amphipathic nature mimics the lipid bilayer but can also destabilize proteins if too stringent. As such, it is important to choose a detergent in which the protein is stable for use in later experiments. The detergents being used are LMNG, DDM, and Digitonin. Of these, LMNG is predicted to yield the largest amount of protein. The protein will then be used to perform a lipid transport assay with the goal of determining the function of YebS and its role in lipid trafficking. It is important to use the same detergent during protein purification as in the assay. Ascertaining this function will help to understand how YebS passes lipids to YebT, making it a possible protein for future development of antibiotics that target lipid transport in E. coli.

Evelyn Cheng

Advisor: Ashlee Plummer-Medeiros

Studying the lipid transfer function of PqiB and YebT

Bacterial membranes are composed of two phospholipid bilayer membranes: the inner and outer membrane. For bacteria to grow, lipids are continuously shuttled from the inner to the outer membrane. This transfer of lipids is affected by phospholipid interaction with membrane proteins and understanding more about this process can contribute to future designs and more effective antibiotic designs. Instead of studying complex bacterial membranes, vesicles are used as a simplified system for analysis; vesicles are composed of an enclosed phospholipid bilayer, which are used to conduct in vitro lipid transfer assays. Donor vesicles contain fluorescent-tagged lipids and acceptors vesicles have no tagged-lipids, therefore the movement of lipids from donor to acceptor mirrors the shuttling between the inner and outer membranes of bacteria. Assays were conducted to specifically observe how different factors such as changes in time, concentration, temperature, pH, and shaking affect transfer activity. As the bacterial membrane contains lipids with two headgroups PE (Phosphatidyl-Ethanolamine) and PG (Phosphatidyl-Glycerol), both were investigated here. Results showed transport activities were similar at all tested temperature and shaking conditions but differed at variable pH and donor/acceptor ratios. Furthermore, lipid transfer assays will be conducted with the insertion of the proteins PqiB and YebT to study their effect on lipid transport. PqiB and YebT are lipid transport membrane proteins that reside in the periplasm and are suspected to connect two vesicles in the lipid transfer assay, therefore it is hypothesized that the lipid transfer activity will accelerate with the addition of PqiB or YebT.

Lily Desiderio

Advisor: Yan Kung

Understanding the Structure and Inhibition of Homosapien Mevalonate Kinase (HsMK) using X-Ray Crystallography

The mevalonate pathway, also known as the HMG-CoA reductase pathway, is a metabolic pathway responsible for the production of isoprenoid precursors.  Isoprenoids are the largest class of naturally occurring compounds, responsible for various functions throughout the body.  In addition, isoprenoids are vital precursors sex hormones.  In this study, the Homosapien Mevalonate kinase (HsMK) mechanism of action, structure, and inhibition will be observed.  HsMK is the fourth enzyme in the mevalonate pathway in humans.  The active site of mevalonate kinase requires two substrates, mevalonate and ATP, to form 5-phosphomevalonate.  While structural images of MK bound to either mevalonate or ATP have been determined for other organisms, it’s structure has yet to be determined in humans.  In addition, the proposed mechanism of action is not supported by the current structures of MK bound to either mevalonate or ATP.  As such, the structure of HsMK bound to both mevalonate and ATP simultaneously is required.  While studying the structure of MK during reaction, a dilemma occurs.  The speed at which the reaction occurs, is too quick to be analyzed via x-ray crystallography.  Thus, in order to visualize the active site of HsMK bound to mevalonate and ATP, an ATP analog must be utilized.  Similar to ATP, ATP analogs will react with mevalonate and the active site, but prevent the reaction from completing.  Thus, HsMK will be locked in an active site bound to mevalonate and ATP.  By studying the active site of HsMK bound to both mevalonate and ATP, the mechanism of can be better understood.  HsMK is regulated via feedback inhibition.  Thus, downstream products in the mevalonate pathway serve as inhibitors to HsMK.  Considering the inhibitory products in the mevalonate pathway vary in size and structure, how does the active site accommodate all of them?  To answer this question, the kinetic activity and structure of HsMK bound to various inhibitors.  To achieve success, techniques such as molecular cloning and mutagenesis, protein expression and purification, kinetic characterization, and crystallization will be employed.

Rosie Dougherty-Herrmann

Advisor: Bill Malachowski

Development of Chiral Nitrogen Containing Drug Intermediates via Birch-Heck Synthesis

Nitrogen-containing rings such as pyridine and pyrimidine are extremely common components of bioactive drugs and drug candidates due to their aromaticity and the intermolecular forces provided by nitrogen. However, aromatic structures like these often participate in side-reactions, leading to undesired side effects and diminished drug effectiveness. Research has shown that tetrahedral carbons have better results in clinical trials due to improved selectivity over flat aromatic structures. The Malachowski lab uses organic synthesis processes, particularly Birch-Heck process, to create chiral drug intermediates. The process begins with a Birch reduction-alkylation reaction that creates a chiral center from benzoic acid and has been successfully done with several different substituents. Eventually, aza-Heck or aza-Wacker reactions can be used to cyclize the added substituents. My research project in Dr. Malachowski’s lab will aim to create nitrogen-containing drug intermediates with chiral centers. Currently, I am working on adapting the Birch reduction-alkylation to alkylate pyridine. This reaction has been successfully performed, but research into the potential of adding various substituents to pyridine via Birch reduction-alkylation have not been thoroughly explored. Pyridine bears resemblance to important biomolecules such as NADH, and reduced versions could therefore provide potential drug candidates. The eventual goal of successful reduction of pyridine could also include the synthesis of swainsonine, a natural product with potential anti-cancer properties.

Christina Douglas

Advisor: Bill Malachowski

The Functionalization of Cyclohexene Rings Through Hydroamination

Oseltamivir is an antiviral prodrug used in the prevention and treatment of influenza. It is a small molecule, consisting of a cyclohexene ring with four attached groups, including an amino group. In research carried out by the Hartwig group, it was demonstrated that 1,3-dienes could undergo palladium-catalyzed hydroamination, adding an amino group and reducing the diene system to a single alkene. The Birch reduction-alkylation reaction produces 1,4-cyclohexadiene-containing structures that may also be susceptible to this process, and which have the added benefit of chirality, a property that can significantly impact how drugs interact with biological systems. The focus of this research, combining the hydroamination process identified by the Hartwig group with a Birch reduction-alkylation, would allow for the creation of cyclohexenes with a variety of attached groups, which could be used to synthesize derivatives of oseltamivir or other compounds with the potential for bioactivity that contain functionalized cyclohexenes.

Taylor Ferreira

Advisor: Jonas Goldsmith

The Synthesis of Bimetallic Catalysts and their Incorporation Into Hydrogen-Based Energy Production

In the United States, hydrogen gas is most commonly derived from harmful fossil fuels through steam methane reforming, which releases carbon dioxide as a byproduct. Sustainably generating and utilizing hydrogen gas as a form of carbon-free energy is the key to a healthier future. This research focuses on the synthesis of a bimetallic molecule which catalyzes the reduction of water by light energy, yielding hydrogen gas. The bimetallic molecule is composed of two transition metal complexes, one of which acts as a photosensitizer (PS) while the other acts as an electron relay (ER). The PS absorbs light energy, becomes excited, and transfers an electron to the ER. The ER then transfers an electron to an acid, ultimately generating hydrogen gas. The excitement of the PS which facilitates this series of electron transfers is brief, therefore it is crucial for the PS and the ER to be in close proximity to one another. A “lock and key” method will be utilized to fix the PS and ER in a position such that they may efficiently react with one another during this limited period of excitement. The two complexes consist of bipyridines bonded to a ruthenium center. The PS and ER can not be connected without the presence of additional functional groups. An amine will be installed to one complex and a carboxylic acid will be installed to another complex allowing them to unite via an amine-carboxylic acid coupling mechanism.

Chelsea Freer

Advisor: Sharon Burgmayer

Synthesis and Optimization of the ligands 2-pivaloyl-6-chloropterin and BMOPP 

Many metals are critical to sustaining life on earth – Iron, Zinc, Copper, etc. One such metal is Molybdenum (Mo). The element forms the catalytic center of a variety of enzymes., which then perform essential reactions such as respiration, protein synthesis, oxidation, and detoxification. This catalytic center, also known as the molybdenum cofactor (Moco), is composed of a Mo atom and a pterin-dithiolene ligand - aka molybdopterin, MPT. The lab focuses on synthetic approaches to create and investigate functions of Moco model compounds. 

I am currently working on the synthesis of 2-pivaloyl-6-chloropterin, in which the pivaloyl group improves the solubility of the system. The next step will utilize a Sonogashira Coupling Reaction to yield 6-(3-butynyl-2-methyl-2-ol)-2-pivaloyl pterin (BMOPP). In addition to synthesizing these materials, I will work on optimizing the procedures to generate a large, pure yield. This goal will be achieved through the mastery of various synthetic techniques including the Schlenk Line and Column Chromatography, as well as analytical techniques such as TLC, NMR, and IR. 

Lana Giha

Advisor: Bill Malachowski

Studies towards the Total Synthesis of Dendrobine via Birch-Heck Sequence

In the Malachowski group there is an interest in using the Birch-Heck sequence to produce bioactive compounds, particularly those inspired by natural products. Using the Birch-Heck sequence we hope to form a bicyclic structure containing a five and six membered ring fused together with a quaternary center forming at one of the bridgehead carbons. This compound is a key intermediate in the synthesis towards dendrobine, a natural product that has exhibited both analgesic and antipyretic effects. Previous syntheses have been developed but all with modest success and relatively low yields. We hope to improve upon these previous efforts.

Hannah Kreider

Advisor: Bill Malachowski

Enantioselective Synthesis of Drug Candidates Through the Birch-Heck Sequence

Recent structural studies of drug candidates have shown that molecules with more tetrahedral, sp³ centers, including chiral ones, are more likely to succeed in clinical trials and eventually become successful drugs. In the Malachowski lab, the goal is to develop a synthetic tool to efficiently create drug candidates with chiral centers in order to reduce these side effects. This summer, I will study the Birch-Heck sequence, a tool that allows the efficient and selective formation of chiral tetrahedral carbons. This sequence begins with the Birch reduction-alkylation reaction to create prochiral sp³ carbons with a variety of substituents from inexpensive benzoic acid and ends with the Heck reaction, which involves an intramolecular desymmetrizing reaction that enantioselectivity creates a cyclic structure with two chiral centers. My research focuses on the addition of alkyl substituents to the bisallylic carbon of the Birch product through radical processes rather than the carboxylic acid, as has been previously done. This allows for the diversification of structures that are able to be made through this Birch-Heck Sequence.

Sydney McDonnough

Advisor: Yan Kung

Investigating the Structure, Kinetics and NADPH/NADH Cofactor Specificity HMG-CoA Reductase of Bordetella petrii

The mevalonate pathway is responsible for making the biosynthetic precursors to all isoprenoids and steroids. In the focused upon mevalonate pathway HMG- CoA reductase (HMGR) is responsible for reducing HMG-CoA to mevalonate and is also the rate determining step in the enzyme pathway. In order to reduce it, it binds the redox cofactors NADPH or NADH and most HMGR enzymes have a cofactor specificity to either of these two cofactors however prior research has shown that Bordetella petrii HMG-CoA reductase (Bp-HMGR) was found to have the ability to use both cofactors and a structure of the enzyme bound to NADH was developed. Thus in my own research I will further investigate the kinetics and catalytic efficiency of Bp-HMGR in the presence of NADH and NADPH to determine which one is favoured by the enzyme as well as using protein crystallisation methods in order to develop a structure of the protein bound to NADPH and determine more specifically which amino acids in the sequence that correlates to the binding region of the cofactor could be contributing to its ability to bind to both NADPH or NADH and how those amino acids could correspond to the enzymes overall preference to either cofactor.

Kirya Miller

Advisor: Patrick Melvin

A Modified Beckmann Rearrangement Using Sulfone Iminium Fluorides (SIFs)

The Melvin group has previously developed a novel class of S(VI) reagent, called sulfone iminium fluorides (SIFs), capable of performing efficient deoxyfluorination reactions in just 60 seconds at room temperature. Work this summer is focused on expanding its use beyond typical deoxyfluorination reactions to mediating a modified Beckmann rearrangement--the rearrangement of an oxime functional group to an amide, often catalyzed by acid--to convert oximes into imidoyl fluorides. My work will expand on this by taking various amidoximes to imidoyl fluorides using SIFs and investigating the reactivity of these intermediates with nitrogen nucleophiles and with water to form guanidine derivatives and urea derivatives, respectively.

Darya Ostapenko

Advisor: Sharon Burgmayer

This abstract outlines a summer research initiative centered on the synthesis and analysis of artificial compounds that emulate Molybdenum cofactor (Moco), a key element in molybdenum-based enzymes. These enzymes are instrumental in a variety of catalytic processes pertinent to oxygen transport, and thus, indispensable to life. My mentor for this venture is Dr. Burgmayer.

A specific focus is on bis(dithiolene)molybdenum complexes, structurally and functionally analogous to Moco in several enzymes such as DMSO reductases. These reductases perform under anaerobic conditions in specific bacteria, crucial for sustaining a balanced human gut microbiome.

This research aims to further ongoing efforts to synthesize a stable bis(dithiolene)molybdenum complex, which is expected to yield critical information regarding the structure, bonding, redox activity, and catalytic mechanisms of molybdenum-dependent enzymes. It is hoped that crafting a steady model will not only advance our research but also offer significant insights to future investigators regarding the functions Moco performs in biological systems.

The implications of this research extend beyond academic curiosity, potentially informing the creation of innovative drugs or treatment approaches for a range of health issues.

Charli Parsons

Advisor: Bill Malachowski

Synthesizing Various Pro-drug Derivatives of Varenicline

The smoking cessation drug varenicline (brand name Chantix) has been in wide use for nearly two decades. As a partial agonist of the nicotinic acetylcholine receptor (nAchR) subtype α4β2, varenicline can reduce withdrawal symptoms in patients discontinuing nicotine use. Large-scale analyses have estimated varenicline treatment’s success rate at between 9% and 20%, with non success frequently due to varenicline’s side effect profile. In order to improve the pharmacokinetics of varenicline, we have synthesized/will synthesize four pro-drug derivatives of varenicline, using various methods of amide coupling along with a wide range of other common synthetic organic reactions. The results of this study show (put results here). With these results in hand, it will be possible to study new smoking cessation treatment plans and finally address the drawbacks of this popular drug.

Malini Rajbhandari

Advisor: Ashlee Plummer-Medeiros

Mutagenesis Study of PqiA to Study the Effects of Hydrogen Bonding on Protein Function

PqiA is a membrane protein found in gram-negative bacteria which is hypothesized to transport lipids between the inner and the outer membrane of these bacteria. However, the protein is not well studied and developing a better understanding of the function of this protein will help with research on antibacterial resistance, as lipid transport is an essential part of bacterial replication and subsequent survival. The goal of this research is to better understand PqiA function by focusing on the protein-lipid interactions. Previously, all-atom molecular dynamics simulations of PqiA were used to study the protein dynamics of various regions of PqiA. These simulations revealed that Hydrogen Bonding is likely an essential part of the protein function. This raises the hypothesis that the specific hydrogen bonding reactions are required for PqiA-mediated lipid transport. Based on the previous analyses, six Aspartic Acids residues were chosen from PqiA which frequently were identified as amino acids that participate in hydrogen bonding. Site-directed mutagenesis was then used to mutate these individual Aspartic Acid residues to Leucine. The Leucines will be similar in spatial structure and size to the Aspartic Acids but lacks the ability to Hydrogen Bond. Mutated proteins will be expressed in E. Coli and their activity will be tested using a functional assay to see how these mutations impact the rate of lipid transport between liposomes. These results will be combined with MD simulation data to better understand the effects of Aspartate-lipid interactions on PqiA function.

Bernie Schintz

Advisor: Jonas Goldsmith

Synthesizing transition metal complexes using vinyl bypyridine ligands to produce polymers with hydrogen producing abilities

This research focuses on creating transition metal complexes using bidentate chelating bipyridine ligands and ruthenium. Transition metal complexes act as photosynthesizers, absorbing light which causes its electrons to move to a higher energy level. These complexes can also act as electron relays, carrying electrons from one place to another. Vinyl groups are attached to the transition metal complexes so that a polymerization reaction can occur. Layering the synthesized polymer sheets allows the transition metal complexes to have a close proximity enabling electron transfer. Historically, hydrogen gas is created by decomposing methane, releasing pollutants into the atmosphere. The ultimate goal of this research is to synthesize a chemical system where water can be converted into hydrogen gas by harvesting light energy. This process is revolutionary as it could possibly create a thin layer polymer product that can be applied to surfaces and generate hydrogen gas without the use of carbon. Photosystems have not been bonded together in the manner explained above, highlighting the importance of the future success of this research.

Eunjeong (Sal) Shin

Advisor: Patrick Melvin

Fluorine is widely used in pharmaceutical drugs, specifically in drug designs where introduction of fluorine atoms can significantly change the molecule’s lipophilicity, solubility, acidity, and basicity. Despite fluorination’s crucial application, not many methods of installing fluorine atoms into the target molecule are available and they still pose challenges.  Recently, our laboratory has reported the use of sulfone iminium fluorides (SIF), a fluorination reagent that provides high yields of fluorinated products with a significantly shorter reaction times compared to other reagents.  Using this SIF reagent, I will synthesize and characterize different fluorinated intermediates via a modified Beckmann rearrangement process.  We will use amidoximes as our primary substrate with the aim to generate various products that are derivatives of guanidine and urea.

Tiffany Xue

Advisor: Jonas Goldsmith

Synthesis of bimetallic transition metal macromolecules for photosensitizer and electron relay pre-connection

The transition towards a low-carbon future necessitates the development of environmentally friendly energy sources, including green hydrogen. However, current hydrogen production methods emit substantial amounts of greenhouse gases, rendering them unsustainable. Electrolysis of water offers promise as a green hydrogen production method, but it suffers from high costs and low output. To address these challenges, our laboratory aims to enhance the photocatalytic water reduction system, thereby increasing hydrogen output. In this system, a light-trapping Photosensitizer (PS) rapidly excites and transfers electrons to an Electron Relay (ER). To optimize this system, a crucial aspect is establishing effective connections between PS and ER within a limited timeframe. The objective of our research is to establish pre-connections between PSs and ERs through amide coupling, accomplished by synthesizing transition metal macromolecules, specifically ruthenium, with carboxylic acid one carbon away on either PS or ER and amine on the other. This research has the potential to make a significant impact on the energy sector and the environment by reducing greenhouse gas emissions and contributing to global climate goals. Additionally, the mechanism employed to attach groups onto the original molecule to establish connections holds further potential for application in other synthesis cases.

Zahraa Zamir

Advisor: Yan Kung

Structural modification of cofactor specificity in HMG-CoA reductase

The mevalonate pathway is an important pathway in multiple biological systems and consists of seven enzymes that act as precursors to the production of steroids and isoprenoids, which are used in many industries. The enzyme HMG-CoA reductase (HMGR), the third enzyme in the mevalonate pathway, binds to either NADPH or NADH to reduce HMG-CoA to mevalonate. Previous research has indicated that a “cofactor helix” near the NAD(P)H binding site is responsible for this NAD(P)H preference, and we have recently shown that switching the entire cofactor helix results in a switching of NAD(P)H preference. Here, I will study the effects of multiple mutations of the cofactor helix to determine exactly which amino acid or combination of amino acids cause the change in cofactor preference. Specifically, I will study D146Y, V148S, and L152R mutations in HMGR from Delftia acidovorans (DaHMGR), and the corresponding inverse mutations in HMGR from Streptococcus pneumoniae (SpHMGR). This will be done through expressing and purifying these mutant proteins, then testing their activities via kinetics studies. If we find that any of our mutants have interesting activities, we will continue protein crystallization to allow us a clearer understanding of the mutant HMGR structure. Through this study, I wish to contribute to a better understanding of the importance of structural basis for HMGR in relation to cofactor specificity.

Ruolin Zhang

Advisor: Jonas Goldsmith

Synthesis of vinyl bipyridine thin films to optimize the photocatalytic water reduction system

In recent years, the demand for clean and renewable energy has increased. A famous example of green energy, hydrogen could be produced from water and light using transitional metal complexes as electron carriers and catalysts. This new method is called a photocatalytic water reduction system. Transition metal complexes would perform as photosensitizers (PS) and electron relays (ER) in electron transfer to help the water splitting. Sacrificial reductant donates an electron to the PS to excite the electron to a higher energy level using light energy. ER acts as the intermediate to carry the energy from the excited electron to reduce water. The interaction between PS and ER is considered a workable application to increase the efficiency of the overall electron transfer and water-splitting reaction. Our research generally aims to form transition metal complexes with vinyl groups attacking and polymerized complexes using electropolymerization. Then, the polymers will be pre-positioned in thin films to achieve the interaction. The proximity of the PS and ER helps to increase the electron transfer rate and reduce energy consumption. Currently, the research focuses on producing and increasing the yield of complex precursors: 4-methoxy ethyl-4'-methyl-2,2’-bipyridine and 4-methyl-4’-vinyl-2,2’-bipyridine, and making a connection between the vinyl precursor and transition metal- Rhodium.

Chiara Zuccoli

Advisor: Sharon Burgmayer

Synthesis of Tungsten Enzyme Models

Molybdenum and tungsten enzymes play a vital role as catalysts in a wide range of organisms, including humans. Studying their chemical properties helps us to better understand their role in important biochemical reactions. The Burgmayer lab’s primary focus is the synthesis and study of molecules containing the catalytic site known as Moco, which includes a molybdenum atom and the pterin-dithiolene ligand. Similar complexes can be synthesized using tungsten in the place of molybdenum with several key considerations to keep in mind, such as its preference to create a trisulfide structure as opposed to molybdenum’s tetrasulfide compound. The synthesis pathway for tungsten models has several obstacles that need to be considered at each step in order to efficiently characterize each synthetic intermediate. An unidentified side product (-704)  that appears at the first synthetic step (tungsten tricarbonyl) might be interfering greatly with yield, so its identification could be useful moving forward. The tendency of the trisulfide-BMOPP complex to spontaneously move to its oxo form makes characterization of the target complex difficult. My goal is to tackle these issues, in addition to several others associated with the synthetic pathway, using techniques requiring a Schlenk line and glove box, as well as analytical tools such as mass spectrometry, IR spectroscopy, and NMR.

Zhuo (Cecilia) Chen

Advisor: Chris Murphy

Debugging Visualization

Locating bugs in software development is a time-consuming and costly process that involves extensive testing, including failing test cases. In the study "Visualization of Test Information to Assist Fault Localization," Jones et al. proposed a method that displays lines of code in different colors based on the likelihood of containing bugs. In this research, we aim to improve upon this approach by introducing two key modifications. Firstly, we propose displaying the code as a Control Flow Graph, providing users with a clear visualization of the code's path likely to contain bugs. Secondly, we suggest using varying colors and sizes for elements in the Control Flow Graph to indicate the likelihood of containing bugs. Drawing upon insights from information visualization and cognitive psychology, our objective is to present information visually, enabling developers to swiftly identify and resolve bugs. To evaluate the effectiveness of our approach, we will conduct two experiments: a user study to assess the efficiency and accuracy of fault identification and an experiment to determine the accuracy of code highlighting for bug localization. The outcomes of this research will contribute to advancing bug visualization techniques and enhancing the efficiency of the debugging process in software development projects.

Joseph Kim

Advisor: Chris Murphy

Experiences of students with different deadline policies in CS classrooms

During the coronavirus pandemic, the dynamics of classrooms underwent drastic changes. Traditional face-to-face class meetings transitioned to remote learning, requiring both instructors and students to adapt to this sudden shift while managing their personal circumstances. Recognizing the challenges faced by students, instructors granted increased flexibility to help them manage their workload. However, as the pandemic recedes and students return to in-person classes, a lingering question persists in both the classroom and institutional settings: to what extent should students be given flexibility?

On one hand, much research demonstrates that providing students with extensions or allowing for late submissions can enhance learning and academic performance, while simultaneously reducing student stress. This approach grants students a greater sense of control and offers better support to nontraditional students in community colleges and online learning platforms who may have extenuating circumstances. On the other hand, a lack of structure can be detrimental to students prone to procrastination, and many students rely on deadlines to stay on track with their coursework. The impact of a deadline policy is particularly significant in the field of Computer Science, where regular assignment submissions are crucial for assessing student learning and providing necessary feedback.

Hence, the objective of this research is to explore the advantages and disadvantages of various deadline policies in Computer Science classes, with a focus on identifying the policy that yields the best outcome for students. This not only includes academic performance but also learning, time management, and mental health of the students. The findings of this study will enable Computer Science instructors to make more informed decisions regarding the structure of their courses, ultimately benefiting their students. To achieve this goal, a survey will be designed to gather student feedback on their experiences with different deadline policies across multiple dimensions. Additionally, an optional comment section will provide participants with an opportunity to provide more detailed descriptions of their experiences.

Wynn Bryant

Advisor: Don Barber

Comparing Stable Carbon Isotope Values Between Underlying Mangrove Sediments and Overwash Layers Deposited by Hurricane Ian in Southwest Florida

Hurricane Ian was a Category 5 tropical cyclone that struck the west coast of Florida in 2022. Its peak winds of up to 160 mph caused considerable damage to Florida infrastructure, economy, and coastal environments. The hurricane also generated intense flooding that deposited allochthonous sediments along the west coast of Florida. My lab is interested in identifying properties of Ian’s overwash deposits that can be used to distinguish them from the underlying non-storm sediments. My project specifically compares bulk stable carbon isotopic composition for this purpose.

Overwash deposits from Hurricane Ian and associated underlying sediment samples were collected along the southwest coast of Florida for examination. My research aims to determine if there is a difference in stable carbon isotope signatures between overwash deposits and underlying mangrove sediments. If there is a clear contrast in stable carbon isotopes, then carbon isotope values can function as a proxy for identifying past storm events buried in the geological record. The sediment samples will be freeze-dried, milled, weighed, and sealed in tin capsules prior to being analyzed in an elemental combustion and cavity ring-down spectroscopy system to measure the stable carbon isotope ratios. I hypothesize that the stable isotopic composition of the  overwash deposits and underlying sediment will differ because the allochthonous storm deposits are likely to include carbon that is isotopically distinct from that of the mangrove sediments.

My results will be combined with other sedimentary, micropaleontological and biogeochemical data to provide a full characterization of Hurricane Ian’s overwash deposit. Evaluating proxies to identify storm deposits is valuable because it allows researchers to reconstruct historical storm surge events in the geologic record, and compare their magnitude and frequency with recent storm records. Ultimately, this leads to a better understanding of the impact of current climate change on storms so coastal advisors can make educated decisions on coastal resiliency and adaptation. 

Morgan Hanson-Rosenberg

Advisor: Selby Hearth

Interpreting the history of metamorphism in the Wissahickon formation using mineralogy and mapping

This summer I am working with the mineralogy of the Wissahickon formation, trying to expose some of the metamorphic history. The Wissahickon formation is a bedrock unit that underlies much of Philadelphia and is defined mineralogically by abundant mica and garnet. The sequence of metamorphic and orogenic events that produced the underlying rocks of the Philadelphia area are strikingly complex and an ongoing area of debate for geologists.

In order to interpret the metamorphic history, I am using existing data on index minerals in the Wissahickon and strategically mapping where certain minerals have been observed in the Philadelphia area. I will also be reconciling thin section mineral analyses with geologic units and outcrops from Southeastern Pennsylvania and Northern Delaware and using QGIS to map thin section mineral data.

My hope is that this project will deepen my understanding of the history of these rocks and result in an interpretation of the sequence of metamorphic events that created the highly divisive Philadelphia area geology.

Samantha Lyster

Advisor: Arlo Weil

Investigating Laramide Orogeny-Associated Shortening Across the Colorado Plateau

The Laramide orogeny was a period of mountain-building on what is now North America, which began in the Late Cretaceous and ended in the Paleogene period. During this period, an oceanic plate subducted under the western edge of North America at a notably shallow angle, an occurrence known as flat-slab subduction. The general understanding is that deformation caused by this event migrated northeast-ward; for example, activity started in the southern Colorado Plateau around 80 million years ago, but in northern Wyoming around 60 millions years ago. This summer, we will be traveling to the Colorado Plateau to collect rock samples to gain a better understanding of strain and stress orientation at various locations associated with the Laramide orogeny. This research helps us learn how continents are deformed by tectonic processes and develops a model for flat-slab subduction.

            In order to quantify shortening directions, we will measure populations of minor faults, both out in the field and from the existing literature. In the lab, we will conduct magnetic susceptibility analyses on the collected rock samples to estimate shortening directions from microscale internal fabrics. We will also use paleomagnetic analysis to quantify any rotation the rock has undergone in order to test whether our measured shortening directions need to be corrected for any post- or syn-tectonic rotations. By investigating stress orientation and shortening directions at many individual localities, we will gain further insight into the big picture of how and when this orogeny occurred.

Adalia Rodriguez

Advisor: Don Barber

Distributions of modern salt-marsh foraminifera in southern New Jersey and their viability for sea-level studies

Currently the United States eastern seaboard is experiencing sea-level rise at a faster rate than the global average. In order to understand the magnitude of local sea-level change and how it may affect coastal habitats and communities in the future, we must look in the past to determine how and why sea level has changed through time. Salt marsh environments, which are prevalent on the US East Coast, can be used to reconstruct past sea level. Although salt marshes often appear flat, there are subtle topographic differences which experience different tidal flooding frequencies. Furthermore, salt-marsh foraminifera species are sensitive to the tidal flooding frequencies, and thus inhabit specific elevation zones within the marsh. Therefore, distinct foraminifera assemblages can be associated with tidal flooding frequency and, hence marsh surface elevation. Characterization of the modern foraminifera assemblages provides a key to interpreting paleo marsh elevation from core samples extracted from older and deeper sediments.

This project will be characterizing the modern salt marsh foraminifera assemblages along two elevation transects across a salt marsh in Dennis Creek, New Jersey. The modern assemblages describe the relative abundances of foraminifera species as a function of marsh surface elevation relative to modern local sea level. In order to analyze foraminiferal assemblages, live and dead foraminifera are counted at each sample site across two transects. The modern foraminifera samples were stained with rose Bengal immediately after collection to differentiate dead and live foraminifera, but ultimately, only dead foraminifera are to be used in analysis. Samples were stored in a buffered ethanol solution and refrigerated prior to analysis. Each sample is wet sieved to isolate the 63-500 µm size fraction, split into eight equal aliquots, and then counted under a microscope in distilled water. In each sample, a minimum of 100 dead foraminifera tests will be counted and identified to species level to observe changes in assemblages across the transects. Ultimately, this data will be used as a modern training set to produce a new sea-level record from Dennis Creek to constrain sea-level variability over time and space. An improved understanding of local sea-level variability is essential for future predictions of coastal inundation by rising seas due to climate change.

Aidan York

Advisor: Arlo Weil

Constructing a History of Laramide-era Tectonism and Deformation in the Colorado Plateau

The Laramide Orogeny is a major deformational, mountain-building event that impacted western North America approximately 80 million years ago due to the low-angle subduction of an oceanic plate under the North American plate. The deformational history of this event, particularly with respect to rigid-body-rotations, translations, and internal strain, is recorded within the remnant paleomagnetism and meso- and micro-scopic structures and fabrics in rocks from the Colorado Plateau, located in the Four Corners area of the United States. Studying this region is of particular interest, as it holds a record of transitioning tectonic environments and mountain-building, spanning before, during, and after the Laramide itself. For my summer research, I am looking to uncover aspects of that history, by quantifying rotations and applying time constraints to the region’s development.  This will be done by conducting paleomagnetic and fabric analyses of samples collected from the Colorado Plateau. In particular, I will be measuring anisotropy of magnetic susceptibility (AMS) to infer Laramide shortening directions based on fabrics of deformed rocks, and studying remnant magnetization to determine the orientation of North America at the time of rock formation.

These analyses will be conducted on samples previously collected by Dr. Weil, as well as on samples our team collects this summer. This summer’s research will include a two-week trip to the Colorado Plateau, beginning in Utah and travelling to New Mexico, to visit several Laramide age field sites, collect more samples for analyses, and record observations about mesoscale deformational features, such as faults and fractures. This field data, in conjunction with laboratory analyses of samples, will help to create a fuller picture of the American southwest’s unique and storied geologic history. This, in turn, will ultimately lead to a better understanding of continental tectonism associated with and resulting from low-angle subduction.

K.c. Kula

Advisor: Victor Donnay

Approaches to Energy Conservation: A Mathematical AnalysisWith increasing threats of global warming and limited non-renewable resources, energy conservation is more important than ever. Our research will focus on energy conservation with geothermal heat pumps and improved insulation. These eco-friendly resources often receive grants and tax credits under the Inflation Reduction Act. We will also work with Liz Robinson, Executive Director of the Philadelphia Solar Energy Organization, to develop and apply her solar toolkit to Pennsylvania school districts. This toolkit encourages schools to use the Inflation Reduction Act to purchase solar panels at lower prices in our changing environment. Using mathematical and differential equations, we will measure the potential cost and energy savings of improved insulation, airflow, and geothermal and solar energy. These methods can help a school district or household save money and energy.

Cordelia Li

Advisor: Leslie Cheng

Stock Price Prediction of Bilibili Stock

During this summer, I will build upon what I learned in the Math B225 (Introduction to Financial Mathematics) course to predict stock prices. The stock market is known for being volatile, dynamic, and nonlinear, so a successful prediction of a stock’s future price would yield significant profit.

In this research, I intend to analyze and predict the stock price of Bilibili, one of China's leading streaming platforms that offers videos on demand such as documentaries, variety shows and other original programming, using various mathematical models such as the Generalized Binomial Model and the Black-Scholes Model.  For example, I will be employing variations of the Hull-White Algorithm and Geometric Brownian Motion to predict stock prices for Bilibili.

Orli McGuire-Berk

Advisor: Victor Donnay

Approaches to Energy Conservation: a Mathematical Analysis

The usage of energy produces CO2 emissions that are harmful to the Earth. Most of that time it feels as though there is nothing you can do on an individual level to help lessen the emission of greenhouse gasses. This summer we are doing an in depth analysis on the ways an individual household can lessen its carbon footprint. Thanks to the Inflation Reduction Act, the government is now giving tax credit for households who take the steps towards using/producing green energy. We will be analyzing geothermal energy pumps, insulation and heat usage in order to figure out a way to balance going green and saving money.

We will also be working with Liz Robinson who is the Executive Director of the Philadelphia Solar Energy Association. They have developed a toolkit for Pennsylvania School Districts on how the Inflation Reduction act can assist them to purchase solar panels. We will be working with her to create educational materials that schools can use to teach their students about solar energy.

Yuxin Wang

Advisor: Leslie Cheng

Mathematical Foundations of Public-Key Encryption: A Revolution in Cryptography

Since the late 20th century, cryptography has undergone a remarkable transformation from being an artistic pursuit of code-writing to a rigorous scientific discipline. This research focuses on the mathematical aspects of public-key encryption, a pivotal advancement in modern cryptography. Previously, ancient cryptography primarily employed private-key encryption, which relied on a shared secret key for both encrypting and decrypting messages. In contrast, public-key encryption introduced a groundbreaking approach by utilizing two distinct keys: a public key for encryption and a private key for decryption.

In public-key encryption, the recipient of a secure message generates a pair of public and private keys. The sender can then use the recipient's public key to encrypt the message, ensuring confidentiality during transmission. The receiver, possessing the corresponding private key, can decrypt the ciphertext to retrieve the original message. The birth of public-key encryption, credited to Diffie and Hellman, brought about a revolution in the history of cryptography. This breakthrough enabled widespread adoption of cryptographic techniques in real-world applications.

This research aims to delve into the mathematical foundations of public-key encryption, exploring the underlying principles and algorithms that ensure its security and effectiveness. We will apply the mathematical principles to real-life examples of public-key encryption.

Jingxuan (Christine) Yang

Advisor: Leslie Cheng

Stock Price Predictions for Apple Technology Company Using Various Models

Accurate predictions of a stock’s future prices are crucial for determining the potential profit it can generate. As one of the largest technology companies in the world, the changes in the stock market of the Apple technology company are of great value to study. We will first employ variations of the Hull-White algorithm to predict future stock prices. Additionally, we shall use Geometric Brownian Motion for Apple’s stock price predictions.

Eva Carmona-Rogina

Advisor: Xuemei Cheng

Creating simulations to examine asymmetric expansion of bubble skyrmions

Throughout the upcoming 2023 summer research program, I plan to apply micromagnetic simulation software to study the formation and behavior of magnetic bubble skyrmions, under the direction of Dr. May Cheng. Bubble skyrmions are topologically protected spin textures that have a circular shape. Their importance in modern science applications involves harnessing their stability, where the application of current can drive their motion. This method can be used to develop high-speed spintronic devices with low energy consumption and high data storage capacity. Research into bubble skyrmions could lead to the development of further miniaturization of digital memory media and computer logic structures.

The ground state of magnetic structure results from energy minimization of the total energy system. This total energy is composed of the summation of the Zeeman (potential energy), DMI (asymmetry), Anisotropic (easy magnetization direction), Dipolar (long-range), and Heisenberg Exchange (short-range) energy terms. By varying the strength of the parameters of these interaction terms, we will be able to model the magnetism of bubble skyrmion formation, where mumax³ software will be employed to develop various simulations.In this summer’s work, I will investigate the asymmetric expansion of bubble skyrmions driven by applied in-plane magnetic fields in [Co(0.5nm)/Gd(1nm)/Pt(1nm)]₁₀ magnetic multilayers. The multilayer system will be modeled, using mumax³, with parameters determined from experimental measurements on [Co(0.5nm)/Gd(1nm)/Pt(1nm)]₁₀ magnetic multilayers. These simulations along with experimental PEEM imaging will provide insight into the asymmetric expansion of bubble skyrmions in the multilayer film.

Yingxiao (Thea) Liao

Advisor: Xuemei Cheng

Fabricating Gold Microdisks for Biomedical Application

Nanomaterials, characterized by sizes of 100 nm or smaller in at least one dimension, exhibit unique properties in comparison to their bulk counterparts, making them valuable across diverse domains such as electronics, medicine, and energy. Two commonly used techniques for fabricating nanomaterials are photolithography and sputtering. Photolithography enables users to design patterns by passing UV light through a photomask to selectively expose a photosensitive polymer that is coated on top of the substrate. During development, the photosensitive polymer is selectively dissolved to expose the desired portions of the underlying substrate. Sputtering is a film deposition method where target atoms are ejected into the gas phase and subsequently deposited as a film onto the substrate.

In this summer’s research, I will use lithography and sputtering to fabricate gold microdisks with nanometer thickness suspended in solution for future biomedical applications. The dimensions of the gold microdisks will be measured through small angle x-ray reflectivity and atomic force microscopy to confirm that they are as designed. The fabricated gold microdisks will be used in future experiments to shed light on the role target geometry plays in phagocytosis.

Lana Maizel

Advisor: David Schaffner

Studying The Effect of A Blocking Disk on Plasma Turbulence and Magnetic Field Lines

Plasma, in the most simple of terms, is a superheated gas which gets so hot that electrons are separated from atoms, forming an electrically charged ionized gas. The majority of the universe is made up of plasma, and this state of matter generally behaves in a chaotic manner called turbulence. Plasma turbulence as a concept is still not yet widely understood, so our experiment seeks to understand how plasma behaves when there is an obstruction placed in front of it. The sun, for example, is composed of plasma, and large gusts of solar winds can extend far past the surface of the sun, carrying plasma to the surface of the moon and beyond. We will model this phenomena in our laboratory by placing a 3 inch x 3 inch ceramic Macor tile in front of the plasma gun within the BMX plasma machine. Since ceramic has no impact on magnetic fields (like the Moon) and can withstand low pressure environments, it is ideal for our experimentation purposes. We predict that, due to the obstruction, there will be no plasma nor magnetic field directly behind the ceramic tile, however we do not know how large this empty gap will be. In a similar vein, we expect both the plasma and magnetic field lines will reconnect some distance away from the obstruction, however the nature of this collision and the state of the turbulence at this collision is still untested. We hope our experiment will provide the scientific community with a greater understanding of not only how certain obstructions can affect magnetic field lines and the path of plasma, but also enrich the scientific understanding of plasma turbulence as a whole.

Nina Martinez Diers

Advisor: Asja Radja

Modeling the Trapping Mechanisms of Drosera capensis

Sundews are carnivorous plants that live in nutrient-poor environments and gain energy by digesting insects. They catch insects in sticky, hair-like cells that cover their leaves, which then signals the overall leaf to fold or curl over the insect, fully digesting it. Once digestion is complete, the leaf reopens back to its original conformation. The underlying mechanism that dictates this folding motion is unknown, however the reversible folding motion has promising implications for the engineering of biomaterials. Known triggers of the trapping motion are chemical stimuli, such as food, or physical stimuli, such as an insect struggling in the hair-like cells. These stimuli induce a variety of trapping motions, including rolling or folding, and our goal is to identify which kinds of stimuli cause which types of trapping mechanism in a handful of different species (all of which have different leaf morphologies). We will then model the morphological transformation of the leaves using particle tracking to analyze time-lapse footage of leaves folding under variable conditions. We will explore how varying the amount of food and the location of food on the leaf results in different trapping motion, and our preliminary results indicate that smaller prey closer to the center of the leaf provoke a folding motion and larger prey closer to the tip of the leaf provoke a curling motion. Finally, we will also use cell-preservation techniques and microscopy to identify what underlying cell changes induce the curvature in the leaf that allows it to trap insects. We hope our model will explain how various triggers induce a variety of trapping motions by tying together leaf geometry, morphological changes, and underlying cellular changes.

Seda Peacher

Advisor: Asja Radja

Turing Patterns in Monkeyflowers

We will be using a modified Gierer Meinhardt model, which is a further developed version of the equations resulting from Alan Turing’s theory of morphogenesis, to model the patterns on the petals of Mimulus, or monkeyflowers. Turing proposed activator-inhibitor equations meant to predict natural patterns, from embryonic development to zebra stripes. His theory was long overlooked, but it has recently captured scientists’ attention. We hope to propose physics-based modifications that will allow models to more accurately represent the actual patterns in the flowers. I will be reproducing and modifying the code from a previous biology experiment using Python. We also hope to find a way to tailor the Gierer Meinhardt equations to these flowers specifically in an attempt to produce more accurate results. I will be testing our modifications in Python as well.

Ellie Rivera

Advisor: Asja Radja

Gorgonian Coral Morphology and Resulting Flow Fields

Coral reefs are integral to marine ecosystems, and rising ocean temperatures resulting from global warming are contributing to coral bleaching and disrupting these systems. Gorgonian corals are the most resilient to climate change, and although the mechanism by which they adapt to these changes isn’t definitively known, it is hypothesized that it may be related to their plastic morphologies and the way they interact with flow fields in their environments. In this project, we will be exploring the flow fields resulting from gorgonian coral morphology using 3D printed model corals in a custom flow tank. Models will be based on scans of live and dried coral samples, and flow fields will be measured using particle image velocimetry (PIV), a technique that uses cameras to record movement oof tracer particles illuminated in a laser plane. Using image analysis in python, we will create velocity maps from this data, which will allow us to understand the flow fields resulting from various gorgonian morphologies.

Sage Thomas and Annick van Blerkom

Advisor: Michael Noel

Density dependence of dipole-dipole interactions among ultracold Rydberg atoms in Stark states

By using laser spectroscopy, Rubidium-85 atoms in a magneto-optical trap can be excited into Rydberg states where they have high principal quantum numbers, n. In this state, the electrons are weakly bound, which allows for energy exchange through long-range dipole-dipole interactions. We have excited the atoms to states within the Stark manifold. Previous studies have investigated the time dependence of this interaction, and we will be investigating the density dependence of this energy exchange.

Anjali Bose

Advisor: Cora Mukerji

Functioning Processes Moderated by Functional Anisotropy in White Matter tract in the Limbic Circuitry

Previous research has demonstrated that prolonged early deprivation has strong effects on neurodevelopment and function. Recent studies have suggested that prolonged exposure to institutionalization in childhood can have lasting effects on the development of white matter, especially in tracts connecting frontal and limbic structures (Kumar, 2014; Bick et al., 2015; Sheridan et al., 2022). Furthermore, frontolimbic white matter tracts have been implicated in the development of internalizing and externalizing behaviors in non-institutionalized adolescents and children who have experienced early institutionalization (Kumar, 2013; Bick et al., 2015; Sheridan et al., 2022), suggesting that these regions are especially important in regards to studying risk for psychopathology (Andre, 2020). The effects of limbic structure on psychopathology can be seen through white matter activity, measured through fractional anisotropy (FA), which indirectly measures white matter structural integrity (Govindan, 2010). The Bucharest Early Intervention program (BEIP) is a randomized control trial that investigates brain and behavioral differences that are influenced by institutionalization and foster care in Romania (Bick et al., 2015; Sheridan et al., 2022). In the BEIP sample, the integrity of the cingulum and the fornix, two structures in the limbic system, have been linked with the development of internalizing and externalizing factors at age 9 (Bick et al, 2015). Sheridan and colleagues found that children exposed to institutionalization had reduced white matter integrity compared to children in never institutionalized groups at 9 years old (Sheridan et al., 2022). Therefore, for my SSR project, I will investigate how structural integrity in white matter tracts connecting frontal and limbic brain areas, specifically the cingulum and the fornix, and associations with the development of internalizing and externalizing factors at age 16 in the BEIP study sample. I will use Diffusion Tensor Imaging (DTI) data, which provides measures of water molecule diffusivity and FA. I hypothesize that there will be a significant association between integrity of white matter tracts in the limbic system, specifically the cingulum and the fornix, and the development of internalizing and externalizing factors of psychopathology. Furthermore, I hypothesize that this relationship will be moderated by group, such that participants reared in the care as usual group (CAUG) with have reduced FA levels in the limbic system white matter tracts associated with the regions of interest compared to the foster care group (FCG) and never institutionalized group (NIG).

Works Cited

Andre, Q.R., Geeraert, B.L. & Lebel, C. Brain structure and internalizing and externalizing behavior in typically developing children and adolescents. Brain Struct Funct 225, 1369–1378 (2020). https://doi.org/10.1007/s00429-019-01973-y

Bick J, Zhu T, Stamoulis C, Fox NA, Zeanah C, Nelson CA. Effect of Early Institutionalization and Foster Care on Long-term White Matter Development: A Randomized Clinical Trial . JAMA Pediatr. 2015;169(3):211–219. doi:10.1001/jamapediatrics.2014.3212

Govindan, R. M., et al. “Altered Water Diffusivity in Cortical Association Tracts in Children with Early Deprivation Identified with Tract-Based Spatial Statistics (TBSS).” Cerebral Cortex, vol. 20, no. 3, 2009, pp. 561–569, https://doi.org/10.1093/cercor/bhp122.

Sheridan, Margaret A., et al. “Early Deprivation Alters Structural Brain Development from Middle Childhood to Adolescence.” Science Advances, vol. 8, no. 40, 2022, https://doi.org/10.1126/sciadv.abn4316.Kumar, Ajay, et al. “Microstructural Abnormalities in Language and Limbic Pathways in Orphanage-Reared Children.” Journal of Child Neurology, vol. 29, no. 3, 2013, pp. 318–325, https://doi.org/10.1177/0883073812474098.

Candy Li

Advisor: Laura Grafe

Contribution of Gonadal Hormones in Orexin Expression and Activation in Female Rats

            Women are twice as likely as men to suffer from stress-related mental disorders such as Major Depressive Disorder (MDD) and Post-traumatic Stress Disorder (PSTD), but the biological mechanism behind the sex differences remains unclear. Orexins are neuropeptides that are important in arousal and the stress response. Specifically, orexins and stress have a reciprocal relationship: orexins promote the stress response and orexins are activated by exposure to stress. Previous research from our lab has shown that female rats have a higher baseline expression, activation, and release of orexins compared to male rats, which contribute to impaired habituation to repeated restraint stress and subsequent cognitive deficits in female rats. However, the mechanism underlying sex differences in orexin expression, activation, and release is unknown. One likely candidate that may explain upregulation of orexins in females is the gonadal hormone estrogen. Importantly, preliminary data demonstrates that estrogen receptors are expressed in orexin neurons and there is a positive correlation between estrogen levels in the blood and orexin activation in the brain in female rats. This project will further explore how gonadal hormones such as estrogen and progesterone affect the expression, activation, and release of orexin. Ultimately, we hope to better understand sex differences in the stress response and inform individualized treatment of stress-related psychiatric disorders.

Catherine O'Connor

Advisor: Cora Mukerji

Relationships between the uncinate fasciculus, executive function and psychopathology in previously-institutionalized youth   

Institutionalization can have negative consequences for development in a variety of domains, including the use of language, cognition, social interactions, executive function, and mental health. Additionally, early life deprivation has shown to impact the structural integrity of white matter tracts in the brain that connect the frontal lobe to the temporal lobe, including the left uncinate fasciculus. Poorer structural connectivity can be measured by reduced fractional anisotropy (Govindan et al., 2010). Reduced fractional anisotropy in the uncinate fasciculus has in turn been associated with internalizing symptoms, such as depression, in adolescence (LeWinn et al., 2014). Further, the poor structural integrity of the uncinate fasciculus due to traumatic brain injury in children ages 6-15 predicted executive function abilities a year after injury (Johnson et al., 2011). In the current study, we will examine the relationship between the structural integrity of the uncinate fasciculus and executive function abilities and symptoms of psychopathology at age 16 using data from the Bucharest Early Intervention Project (BEIP). The BEIP randomly assigned young children in institutional care in Romania to receive a high-quality foster care intervention or to remain in the institution. Exploring relationships among behavioral, emotional, cognitive and neurological outcomes related to the early environments of the participants has the potential to (a) highlight how variation in white matter structure is related to individual differences in self-regulation and emotion regulation and (b) examine the potential remedial effects of early caregiving interventions. To examine the relationships between the structural integrity of the uncinate, executive function, emotional regulation and internalizing symptoms, we will use previously-collected data obtained through Diffusion Tensor Imaging (DTI), a technique that measures the movement of water along a neuron’s axon. We expect that greater fractional anisotropy will be associated with enhanced behavioral, cognitive and emotional regulation and fewer internalizing symptoms. We further expect these relationships to be moderated by early caregiving experiences. In addition to revealing the influence of the uncinate fasciculus on emotional and behavioral outcomes in adolescence, this research may demonstrate the importance of early interventions to address the detrimental impacts of poor caregiving environments on development.

Maya Peiris

Advisor: Laura Grafe

The Effect of the Menstrual Cycle on Stress, Coping, and Sleep in Women

Stress-related disorders such as Post-Traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) are twice as common in women compared with men. Importantly, the increased incidence of these disorders in women arises with puberty and lessens with the onset of menopause, suggesting that cyclic fluctuation of sex hormones (such as estrogen and progesterone) during the menstrual cycle may contribute to stress disorders. Another important factor that may affect vulnerability to stress is the type of coping strategy used to deal with the stressor. For example, maladaptive coping mechanisms such as avoidance can lead to sleep impairments, which is a key symptom of stress disorders. To better understand how the menstrual cycle and coping strategies affect stress and sleep in women, our lab collected subjective and objective data from 49 college aged participants across their menstrual cycle.  Specifically, we used questionnaires and Fitbits to track their menstrual cycle and measure stress, coping, and sleep over the span of 5 weeks. Analyzing the collected data, we hope to answer the following questions: How/do coping strategies change over the menstrual cycle and what impact does this have on stress and sleep? How is sleep affected by stress and how does this change over the menstrual cycle? How/is heart rate variability correlated with stress and sleep during the menstrual cycle? In broadening our understanding of how stress, sleep, coping strategies, and the menstrual cycle intersect, we can provide insight into improving treatment of stress-related disorders in women.

Doudou Tshiyena

Advisor: Cora Mukerji

Links between inhibitory control and frontostriatal and frontolimbic circuits in previously-institutionalized children

Executive functioning refers to the set of cognitive processes that allow someone to self-regulate based on their ability to apply working memory, flexible thinking and self control to their daily tasks. Inhibitory control is included in this set of processes, as it is the skill of effectively regulating automatic responses and selecting a response that is appropriate for a given situation (Diamond, 2013). Learning how to exercise inhibitory control is necessary for self-regulation but can be disrupted and moderated by unconventional caregiving experiences through adverse childhood experiences (Ji and Wang, 2018). Previous research has suggested important neural circuitry, such as frontostriatal and frontolimbic circuits, involved in inhibitory control are compromised in children with histories of institutionalization (Bick et al. 2015; Sheridan et al., 2022). Researching the link between brain structure and executive functioning processes is necessary to understanding how children in adverse environmental contexts develop self-regulation abilities.  The Bucharest Early Intervention Project (BEIP) is a longitudinal randomized control trial meant to research the effects of early caregiving (high quality foster care versus remaining in case as usual) on the development of previously-institutionalized children, provides a unique opportunity to understand complex relationships between white matter development, inhibitory control, and early caregiving adversity. Using BEIP data, I will be examining relationships between white matter development and  inhibitory control in adolescence and whether these are moderated by caregiving experiences. Through diffusion tensor imaging data from the BEIP study, we will analyze the integrity of the white matter tracts and their associations with inhibitory control in later adolescence (age 16). I predict that there will be a link in the abnormalities of white matter and individual differences in children’s inhibitory control and that the strength of this relationship will be moderated by early caregiving environments. It is necessary to study the impact of institutionalization on development as it could mitigate the negative effects deprivation may have on the cognition, behavioral and mental health of children impacted.

Serena Xu

Advisor: Laura Grafe

Sex Differences in the Effect of Orexin Inhibition in the Orbitofrontal Cortex on Cognitive Flexibility Under Stress in the Rodent Model

Panic disorder, Major Depressive Disorder (MDD), and Post-Traumatic Stress Disorder (PTSD) are stress-related disorders that are twice as common in women. Importantly, a decline in cognitive flexibility is a key phenotype in these disorders, with women showing worse impairments. However, the neurobiological mechanisms behind this sex difference remains unknown. Previous studies in the lab have shown that high levels of the neuropeptides orexins impair cognitive flexibility and stress in female rats, and impaired cognition is remedied after orexin inhibition. However, the mechanism by which orexin acts on the brain to cause cognitive inflexibility is unknown. Previous research has revealed that the orbitofrontal cortex (OFC) is employed during cognitive-flexibility-related tasks such as the attentional set-shifting task and the reverse-learning tasks, and that the task performance would deteriorate if subjects had OFC impairment. A major manifestation of such cognitive flexibility decline is perseveration, where the individuals would fail to learn rules for a new task in the paradigm. Our research aims to fill in the gap of knowledge by examining whether orexins act on the OFC to impair cognitive flexibility in female rats after stress. Importantly, studies show that the orexin type-1 receptor (OX1R) is present in several subregions of the prefrontal cortex (which includes the OFC). Thus, we will administer an OX1R antagonist targeting the OFC to inhibit orexin action in both male and female rats prior to restraint stress and test their subsequent cognitive flexibility in an attentional set-shifting task. We hypothesize that inhibition of OX1R in the OFC will improve overall cognitive flexibility in female rats after stress. As rats have a high genomic resemblance with humans, our results will be translatable to inform society about the reliability of the current FDA-approved orexin antagonist medications in affecting cognitive flexibility.