Summer 2017 Sciences
Presenter Name
Title of Presentation
Mone Anzai
Genetically Engineered Microbiota Will Confer Pesticide Resistance to Drosophila melanogaster
Chris Bartelt
Changes in Abundance of Bacteria with Different Ecology in Soil
Chris Batterman
Chronic Shock Stress (CSS) as a paradigm for inducing anxiety-like behavioral phenotypes in animal models
Corin Bell
The type 2 diabetes drug Metformin inhibits proliferation of cancer cells and modulates T cell activation in vitro
Conrad Bhamani
Optogenetic inhibition of basal ganglia output affects directional licking behavior in mice
Nathan Braswell
Preprocessing Metabolomic Data
Jazmin Campos
VE-cadherin endocytosis is required for endothelial cell migration and vascular patterning
Dipro Chakraborty
Use of PCA and PLSR Computational Tools to Analyze CPC Expression Patterns and Model Pediatric CPC Function
Mandy Chan
Prion Delivery via DNA Co-assembly: the Inside-out Virus
Po-Han Chen
Optogenetic inhibition of basal ganglia output affects directional licking behavior in mice
Ronald Cornely
Dynamin Isoforms show differential Tight Junction Localization in Alveolar Epithelial Cells
Kenneth De Jesus
Functionalizing a Glass Surface with Notch-activation Ligands via Biotin Streptavidin
Luke del Balzo
Rheological Properties of Sickle Erythrocytes
Rohan Dhamsania
To study the neurophysiological disruptions in mice caused by lowdose exposure of Pyrethroid and relevant to risk for psychiatric disorders like Attention-deficit/hyperactivity disorder (ADHD).
Dian Ding
Stereoselectivity of Tungsten Catalyzed Cyclization of 3,4-cis and trans benzylidine alkynes
Yimeng (Lina) Du
Visual Recovery Following Optic Nerve Crash in TRIF Deficient Mice
Liz Enyenihi
Functional Analysis of EXOSC2/Rrp4 Mutants Linked to Disease in Saccharomyces cerevisiae
Jenny Feng
Development of a Brazilian Peppertree Extract with Anti-virulence Activity
Ronnie Festok
Exploring the Dynamic Chemistry of Emergent Peptide Templates
Joseph Fonseca
Use of biomaterial cues to enhance cardiac biological pacemaker function
Somnath Ganapa
Actin Filaments' Role in Human Respiratory Syncytial Virus Assembly by Cryo-EM
Jeff Gao
Recurrent Neural Network Model for Fly Behavioral Transitions
Julia Gensheimer
Role of Glucocorticoid Signaling in CD8+ T Cell Function
Camille Hanes
Investigating the Potential of CaMKII to Rescue Lethality in dNab2 Homozygous Mutant Drosophila melanogaster
Chad Hicks
Developing the Molecular Constituents for Templated-Assembly of N,O-Acetal-Linked Polymers
Mengtong Hu
Investigating the role of LCMT-1 in Hematopoiesis by Using a Conditional Knockout Mouse Model
Soyon Hwang
Visualizing Brain Oscillations During Natural Interactions in Prairie Voles
Alexa Iannitelli
Identification of Neural Circuitry Associated with Psychosocial Stress-Induced Cocaine Seeking in Rats
Connor Innes
Genes associated with phase variation from translucent to opaque colonies in Acinetobacter baumannii
Daniel Jacobs
Characterizing Human CPCs
Jaewon Jeong
Targeting Neuroinflammatory Signaling Pathway to Block the Epileptogenic Effect of Early-Life Seizures
Kaleena Jesson
Long Term Vascular Regeneration After Traumatic Brain Injury
Xinyi Jiang
Effects of liquid extensional properties on the formation of giant soap films
Mengtian Jin
Big Data & Data Interface For Nursing Research
Joohee Kang
Effects of Device-Guided Slow Breathing on Hemodynamics in PreHypertensive Post-Traumatic Stress Disorder Patients
Saumya Karne
Cocaine sensitization in mice lacking β-arrestin2 in D1- or D2containing cells
Benjamin Kasavan
Local Glass Transition Temperature Tg(z) Profile in Polystyrene next to Polybutadiene With and Without Plasticization Effects
Umar Khan
Finer Time Resolutions Hold More Information in Motor Cortical Spiking
Spencer King
Pendrin Gene Ablation Activates the Thiazide-Sensitive Cotransporter
Carli Kovel
Modulating the Catalytic Activity of First-Row Transition Metal Complexes with Redox-Active Ligands that Incorporate Hydrogen Bonding Interactions
Kaela Kuitchoua
The effects of maternal care on the structural development of brain reward circuits
Jayanth Kumar
Effect of chemotherapy drugs on murine breast cancer, lung cancer, and immune cells
Aliana Lawrence
Lymphatic cell functional response and morphogenesis under flow in an abmormal lymphatic environment
Wei-Hsuan Lee
Investigating transgenerational genetic interactions between an RNA binding protein, dNab2, and planar cell polarity components in Drosophila melanogaster
Kathy Li
Functions of KLF5 in Chemosensitivity of Mesenchymal Triple Negative Breast Cancer Cells
Valerie Linck
A mitochondrial defect in the ion channel, VDAC3, alters ENaC activity via ROS
Eva Liu
Low temperature high-resolution spectroscopy of optically active quantum dots in atomically thin materials
Solana Liu
Acute Effects of D2 Receptor Agonist Sumanirole on Microglia Polarization after Ischemic Stroke
Haleigh Machost
Synthesis and Purification of Disubstitution Triazoles via C-H Activation
Caroline Maguire
IL-1 Signaling Mediates Costimulation Independent Rejection
Alicia May
Role of ERK1 Signaling Pathway in Regulating Sodium Excretion through Renal Sodium Chloride Co-transporter (NCC)
Micaela McCall
Acute and Chronic Deep Brain Stimulation Effect on Heart Rate Variability
Jennifer McGuire
Exploring the Effects of Adsorbed Layers on the Glass Transition and Physical Aging
Sanket Mehta
Intracellular delivery of labeling probes using a novel microfluidic approach
Hayley Moyer
IL-6 Activates the Mineralocorticoid Receptor via the JAK2/STAT3 Pathway, Increasing Sodium Chloride Cotransporter Expression
Judith Ogbue
Does Maternal Singing Increase Attention Holding in the Fetus?
Javier Omar
Gamma-aminobutyric Acid (GABA) and Executive Function in Healthy Older Adults
Eddy Ortega
The Synthesis of (1S,3R,4R)-ethyl 1-((tert-butoxycarbonyl)amino)-3fluoro-4-hydroxycyclopentanecarboxylate From Hippuric Acid As A Precursor For PET/CT Scan Imaging Modalities In Cervical Cancer Patients
Samuel Raines
Microfluidic Delivery of Fluorescent Antibodies via Mechanoporation for Differentiation of Cancer Cell Lines and Immune Cells
Divyaansh Raj
The Effect of IL-6 and CRP on the White Matter Tracts of Patients with MDD
Whitley Ramirez
Development of First-Row Transition Metal Complexes for the Aerobic Oxidation of Catechols
Sarah Renahan
A study of reproductive capacity in galactose-1-phosphate uridylyltransferase (GALT)-null Sprague Dawley rats
Samantha Rudin-Rush
The Role of ATP7a in Drosophila Neural Development and Function
Daniel Salgueiro
Kinetics of Rhodium(III)-Catalyzed Allylic C-H Amination of Disubstituted Olefins
Simone Salter
Dialysis Provider Knowlege of Change in the New Kidney Allocation System and the Transplant Process
Brycen Saunders
Use of PLG Nanoparticles to Treat Neuroinflammation and Epilepsy
Alec Shannon
Behavioral and Neurochemical Outcomes of Restored Norepinephrine Synthesis in Noradrenergic Cells in a DOPAResponsive Dystonic Mouse Model
Preston Sheng
Exploiting Drosophila to examine RNA exosome-linked disease
Anika Sinha
Regulation of wzz2 Promoter Activity and Protein Levels at 25°C and 37°C in Pseudomonas aeruginosa
Austin Slone
Exercise Mediates Anesthetic Emergence and Recovery in Diabetic and Control Rats
Houston Smith
The Temperature at which CO is Liberated from Methanol Ice
Kiandra Smith
Investigation of dNab2 Loss in D. Melanogaster Causing Changes in Sleep/ Circadian Rhythms
Lindsey Sniffen
The effect of high fat high fructose diet on peripheral immune cell trafficking into the brain
Hanyao Sun
Optimization of Sequential Grooming in Drosophila
Grace Swaim
Acentrosomal microtubules contribute to collective cell migration
Jordan Swanier
Comparative Phytochemical Analysis of Citrullus ecirrhosus and Citrullus mucosospermus using HPLC and LC-MS
Jaleyah Walker
Does Maternal Singing Increase Attention Holding in the Fetus?
Marshall Weber
Pt(II) CNC Pincer Complex as Catalyst for Alkenyldiol Cyclization
Shaniece Wilson
Fluid Attenuated Inversion Recovery (FLAIR) Imaging Overestimates Lesion Extent in the Orbitofrontal cortex of Rhesus Macaques
Linda Wu
Investigation on the Effect of Different Organic Cover Crop Techniques on Soil Fertility and Microbial Diversity.
Sarah Ye
A transgenic mouse model for studying spermatogenesis and genome instability
Kara Ye
End Stage Renal Disease and Hypertensive Patients Have Altered Pattern of Heart Rate Variability Responses to Graded Lower Body Negative Pressure
Paul Young
Characterization of Diguanylate Cyclase-containing GlobinCoupled Sensors Involved in Bacterial Biofilm Formation
Huiying Zhu
Application of Global Optimization to Image Registration
Ruomin Zhu
Gravitational Waves from Charged Black Hole Binaries
Mone Anzai Genetically Engineered Microbiota Will Confer Pesticide Resistance to Drosophila melanogaster Mone Anzai, Hussein Halemeh, Munsa Manandhar, and Ichiro Matsumura, PhD, Emory University Abstract not available.
Chris Bartelt Changes in Abundance of Bacteria with Different Ecology in Soil Chris Bartelt, Dr. Erika Diaz-Almeyda, Dr. Nicole Gerardo Through beneficial, symbiotic relationships, microorganisms play vital roles in the lives of other species. In an effort to understand the intricacies of symbiotic relationships, I am studying the bacterial symbiont Burkholderia of the squash bugs (Anasa tristis). This symbiont has been shown to be picked up by the bugs from their surrounding soil environment. My specific goal is to investigate the growth of different Burkholderia strains, as well as a pathogenic Serratia strain, over time in soil. To answer this, I used a technique called “mark-recapture,” where GFP-labeled bacteria were inoculated into sterile soil and then withdrawn and plated, on low nutrient media (YG Kanamycin IPTG) plates in a controlled-temperature environment. We compared three strains: Sq4a is the main squash bug symbiont while Smt4a is a strain of environmental Burkholderia found only rarely in squash bugs. Serratia is a pathogenic strain. By determining differences in growth rates of these three strains with this procedure, we aim to understand how the Sq4a strain can become engaged in a symbiotic relationship, while the others do not do so with this particular species of squash bugs.
Chris Batterman Chronic Shock Stress (CSS) as a paradigm for inducing anxiety-like behavioral phenotypes in animal models Chris Batterman, Donald G. Rainnie, PhD. Animal models are crucial to our understanding of disorders relating to fear and anxiety. Paradigms such as Chronic Shock Stress (CSS), Chronic Restraint, and Chronic Social Defeat Stress have been widely used by researchers to induce reliable behavioral phenotypes in animal models that allow us to delve further into understanding the neural underpinnings of clinical disorders. Over the course of a review for a paper in which we used a CSS paradigm, one reviewer questioned the unpredictable nature of the stressor. While CSS paradigms are widely used in research because animals are thought to be unable to habituate to the stress, this reviewer suggested that because our paradigm involved the same chamber being used daily, rats would be able to habituate to the predictability of the paradigm. The reviewer thought that this habituation might have contributed to our results—results that showed no significant behavioral difference between shocked and control groups 5 days after the paradigm—and called into question
whether a stress or anxiety-like state was truly induced by CSS, and whether this paradigm contributed to observed changes in cell properties at timepoints beyond the CSS. This study addresses these concerns and quantifies the stressful nature of our CSS paradigm. An analysis of daily fecal boli and freezing behaviors during the paradigm, as well as of context-induced freezing and anxiety-like behaviors 5 days post-CSS, suggests that our paradigm results in minimal habituation and successfully induces a stable, anxiety-like behavioral phenotype in the animal models.
Corin Bell The type 2 diabetes drug Metformin inhibits proliferation of cancer cells and modulates T cell activation in vitro Corin Bell, BS candidate, Spelman College; Luis E. MuĂąoz, PhD candidate, Emory University; Ramireddy Bommireddy, PhD, Emory University; Periasamy Selvaraj, PhD, Emory University Abstract not available.
Conrad Bhamani Optogenetic inhibition of basal ganglia output affects directional licking behavior in mice Conrad Bhamani, Cornell University; Po Han Chen, Emory University; Arthur Morrissette, Emory University; Dieter Jaeger, PhD, Emory University. Abstract not available.
Nathan Braswell Preprocessing Metabolomic Data Nathan Braswell, Vicki Hertzberg, PhD I have been tasked by my PI to write 2 scripts. the first script, process.r will rename samples of mass spectroscopy urine data and clean up the data. The second script, pvals.py, will run statistical analyses on these preprocessed samples, giving a p-value for each mass/charge value of the data. the result is formatted into a spreadsheet, which can be further processed by Mummichog (a python-based program) to discover exactly which metabolomics play a key role in the process.
Jazmin Campos VE-cadherin endocytosis is required for endothelial cell migration and vascular patterning Jazmin Campos, Cynthia Myers, PhD, Robin Schmidt, PhD, and Andrew P. Kowalzcyk, PhD Abstract not available.
Dipro Chakraborty Use of PCA and PLSR Computational Tools to Analyze CPC Expression Patterns and Model Pediatric CPC Function Dipro Chakraborty; Farnaz Shoja-Taheri, Ph.D., Emory University; Michael E. Davis, Ph.D., Emory University Congenital heart defects (CHDs) can lead to heart failure instigated by the myocardium being unable to satisfy metabolic needs. Specialized cardiac progenitor cells (CPCs) can differentiate into mature cardiomyocytes to promote regenerative effect. Computational modeling can efficiently process complex data sets and data driven networks. This project focuses on utilizing principal component analysis (PCA) and partial least squares regression (PLSR) computational tools to examine CPC expression patterns and model CPC function. Use of PCA will help to compress the scope of the data by reducing the number of dimensions from the original set of variables. The usage of PLSR assists in making a model for predicting cardiac outcomes. Traits and characteristics of expression patterns covary together in an identifiable manner to detect signals. The goal is that estimates can be formed about possible therapeutic functions to address heart defects. Aims of the project include harnessing computational analysis to scrutinize CPC expression patterns by compressing the large sets of data to manageable, relevant covariates. Exosome and cellular cardiosphere-derived cell (CDC) and CPC groups are both investigated to ascertain potential similarities and differences among the two in achieving positive cardiac outcomes.
Mandy Chan Prion Delivery via DNA Co-assembly: the Inside-out Virus Mandy M. Chana, Allisandra K. Rha, Yonggang Ke, and David G. Lynn A hallmark of Alzheimer’s Disease (AD) is the amyloid-beta plaque found in patients’ brains. It has been shown that a congener of this peptide can form stable multilamellar nanotubes in coordination with nucleic acids. Recent study has also shown effective cellular uptake of DNA nanostructures. These discoveries present the opportunity to understand the peptide-DNA interaction in AD and potentially extend to the development of a prion delivery system using DNA. To access this delivery system using the co-assembly and to follow the co-assembly intracellularly, rhodamine 110 and Cy-3 were conjugated to the peptide and DNA, respectively. Co-assembly of these peptides and DNA produced both fibers and multilamellar nanotubes at 37°C. This heterogeneity makes it difficult to confidently attribute any cellular uptake event to
the fibers or the multilamellar tubes in cell assay experiments. Therefore, further optimization of the assembling conditions is necessary to promote homogeneity.
Po-Han Chen Optogenetic inhibition of basal ganglia output affects directional licking behavior in mice Po-Han Chen Conrad Bhamani Arthur Morrissette Dieter Jaeger, PhD, Emory University Abstract not available.
Ronald Cornely Dynamin Isoforms show differential Tight Junction Localization in Alveolar Epithelial Cells Ronald M. Cornely, Emory University; K. Sabrina Lynn, Emory University; Michael Koval, PhD, Emory University Abstract not available.
Kenneth De Jesus Functionalizing a Glass Surface with Notch-activation Ligands via Biotin Streptavidin Kenneth De Jesus, Department of Mechanical Engineering, University of Puerto Rico, MayagĂźez, PR; Matthew Robeson, M.S., Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University School of Medicine; Michael Cardiac disease stands as the major cause of morbidity and mortality worldwide, where myocardial infarction leads to irreversible loss of cardiac myocytes. To aid the problem of tissue loss and reestablishing cell response for tissue regeneration at the myocardium, different treatments have been deployed. Thus, the usage of cardiac progenitor cells (CPCs) has demonstrated promising outcomes to address the problem. Notch1 signaling plays a critical role in cardiac development and differentiation of cardiac stem cells/progenitor cells (Boopathy et al., 2014). Therefore, this work suggests the functionalization of a glass surface with Notchactivation ligands via Biotin Streptavidin conjugation to investigate the mechanism of Notch activation in CPCs. With this, it will be possible to move on to the use of molecular force probes consisting of DNA hairpin structure, which are tethered at one end and functionalized with a ligand at the distal end using Biotin Streptavidin association. The purpose of the work is to measure the force required to achieve a successful Notch activation. Having this, the objective is to propose a novel bioactive, injectable and degradable hydrogel that contains immobilized Notch ligands.
Luke del Balzo Rheological Properties of Sickle Erythrocytes Luke del Balzo, Emory University; Satheesh Chonat, MD, Emory University and CHOA, Wei Li, Ph.D, Emory Unviersity and CHOA; Clinton Joiner, MD/PhD, Emory University and CHOA Sickle Cell Disease (SCD) is the most common hemoglobinopathy affecting over 100,000 Americans and millions of people worldwide. Sickle hemoglobin is normally functional and soluble when oxygenated, but forms insoluble polymers upon deoxygenation (“sickling”). This intracellular polymerization of hemoglobin results in the loss of normal deformability and adversely affects the red blood cell (RBC) cytoskeleton, resulting in hemolysis and shortening of its life span. Whole blood from sickle cell patients contains variable fractions of mature RBCs, reticulocytes, irreversibly sickled cells, and discocytes. We are aware that these cell fractions, to some extent, contribute to the overall cytoskeletal abnormality and pathophysiological effects seen in these patients; however, it is unknown if the fractions contribute equally to the abnormal rheology, or if a single fraction is particularly responsible. In order to study the various RBC fractions, we separated whole sickle blood into density fractions using an OptiPrep™ discontinuous gradient. Each RBC fraction is localized to a specific density (as confirmed by MCHC measurement via Complete Blood Count) and was extracted and washed. We then analyzed each fraction samples using ektacytometry. Ektacytometry is a highly sensitive test in which elongation index (i.e. deformability) in RBC membrane disorders are analyzed via Laser Assisted Optical Rotational Cell Analyzer (Lorrca®). Analysis of sickle density fractions show that the 1.105g/ml fraction -containing irreversibly sickled cells- has a decreased elongation index compared to normal blood of the same fraction. This suggests that the 1.105g/ml RBC fraction is responsible for the abnormal rheology of whole sickle blood.
Rohan Dhamsania To study the neurophysiological disruptions in mice caused by low-dose exposure of Pyrethroid and relevant to risk for psychiatric disorders like Attention-deficit/hyperactivity disorder (ADHD). Rohan K. Dhamsania, Emory University; James P. Burkett, PhD, Emory University; Shannon Gourley, PhD, Emory University; Gary W. Miller, PhD, Emory University Pesticides are biocidal chemicals used in agriculture, household use and horticulture. Due to their mechanism of action as neurotoxins (despite widespread approval for use as pesticides), pesticides have been linked with neurological disorders like autism, Alzheimer’s, Parkinson’s Disease and ADHD. Pyrethroids are a specific class of Environmental Protection Agency (EPA) approved neurotoxic pesticide. Previous experiments from our lab have established a correlation between pyrethroid exposure and ADHD in children. Our lab had also shown that developmental exposure to pyrethroids in mice, at low-doses considered safe by EPA, cause changes in dopamine (DA) system and ADHD related phenotypic responses. Since pyrethroids cause changes in DA system, a full understanding of changes in neurophysiology of DA cells, synapses and vesicles caused by low-dose developmental exposure to pyrethroids would provide critical insights in our knowledge regarding the effects of this toxic exposure, and how it relates to risk for autism, ADHD and other psychiatric disorders. The studies outlined in this proposal will
provide critical information regarding the molecular and cellular alterations caused by pyrethroid exposure, which will be directly relevant to potential therapies. These studies can also lead to changes in regulation policies that may have a direct positive impact on public health.
Dian Ding Stereoselectivity of Tungsten Catalyzed Cyclization of 3,4-cis and trans benzylidine alkynes Dian Ding, Andrew J. Ephron, Frank E. McDonald, Department of Chemistry, Emory University, Atlanta, GA, 30322 The McDonald laboratory recently discovered epimerization of a chiral center in conversion of aldehyde to alkyne. We have now found that the Colvin rearrangement is a superior alternative for this conversion, proceeding without epimerization. Tungsten-catalyzed cycloisomerizations of the resultant cis and trans-substituted benzylidene alkyne were performed to investigate the ring-size selectivity of tungsten cyclization. Cis-substituted benzylidene substrates favor the formation of six-membered ring products, whereas the trans-substituted benzylidenes favor the seven-membered ring products. These results demonstrate that the ring-size selectivity arises from the stereochemistry of the alkynol substrate.
Yimeng (Lina) Du Visual Recovery Following Optic Nerve Crash in TRIF Deficient Mice Yimeng (Lina) Du, Elena Sergeeva, PhD, Taylor Doolittle Optic Nerve Injury induces neurodegeneration both in the retina and the visual structures of the brain. Major signaling pathways involved in optic nerve crush injury has been identified [1]. In addition to the identified pathways, the TIR-domain-containing adapter-inducing interferon- β (TRIF) adapting solely to toll like receptors (TLR)-3 may also play an important role in postONC neurodegeneration of the optic nerve and retina due to its mediation of inflammatory TLR3 signaling when overexpressed. We hypothesize that TRIF knock-out mice will have reduced inflammation and neurodegeneration, better neuroprotection in the retina and optic nerves well as better recovery of visual function following ONC compared to those of wild type mice. This study will allow us to gain more understanding of the role of the TRIF pathway in the optic nerve and retinal neurodegeneration. Since the TRIF pathway is commonly involved in the innate immune response in the brain, our study will also further visualize its role in the central nervous system.
Liz Enyenihi Functional Analysis of EXOSC2/Rrp4 Mutants Linked to Disease in Saccharomyces cerevisiae Liz Enyenihi, Emory University; Milo B. Fasken, Ph. D, Emory University; Anita H. Corbett, Ph. D, Emory University The RNA exosome is a key member of the RNA quality control process that regulates multiple classes of RNA. It is made up of ten core subunits, and RNAs are thread through the central channel of the barrel to the ribonuclease at the bottom to be degraded or processed. The exosome is highly conserved among eukaryotes and was first identified and studied in budding yeast. Recently, mutations in the exosome cap subunit gene EXOSC2/RRP4, have been linked to a neurological disease. This novel syndrome is characterized by retinitis pigmentosa, hearing loss, premature aging, and mild intellectual disability. To study the functional consequences of mutations in EXOSC2, we generated the corresponding amino acid substitutions in the budding yeast ortholog of EXOSC2, RRP4, and analyzed the function of these rrp4 mutants in S. cerevisiae cells. Solid media end-point and liquid culture assays were used to assess whether the rrp4 mutant cells exhibit altered growth rates compared to wild-type cells, and the disease mutations were found to either cause a growth defect or lethality. We also examined the steadystate level of certain RNA exosome target transcripts in rrp4 mutant cells to assess whether mutation affects RNA exosome function. Immunoblotting was used to demonstrate that the mutant protein was indeed expressed whether or not the wildtype RRP4 protein was also being expressed. These data from yeast can help begin to elucidate how the patient mutations cause distinct diseases and tissue impairments in humans.
Jenny Feng Development of a Brazilian Peppertree Extract with Anti-virulence Activity Jenny Feng, Emory University; James T. Lyles, PhD, Emory University; Kate Nelson, Emory University; Cassandra L. Quave, PhD, Emory University The versatility and efficacy of antibiotics has led to them being a cornerstone of treatment for many patients. However, this increased use of antibiotics has led to an increase in antimicrobial resistance (AMR) as bacteria evolve and develop mechanisms to render many antibiotics ineffective at a much faster rate than new antibiotics are being discovered. Staphylococcus aureus, particularly Methicillin-resistant Staphylococcus aureus (MRSA), is already a cause for concern. MRSA alone was responsible for 80,461 invasive infections and 11,285 deaths in the United States in 2011. In efforts to develop novel treatments for MRSA infections, Emory’s Quave Research Group is looking to traditional medicinal plants. In traditional Brazilian medicine, Schinus terebinthifolia Raddii, Anacardiaceae (Brazilian peppertree) has long been used to treat skin infections and wounds due to its antiseptic and anti-inflammatory properties. Our lab has previously determined that an extract of this plant’s fruits exhibits significant quorum sensing inhibitory activity (quorum quenching) against MRSA. Quorum sensing is a system of signaling between bacteria that directly mediates MRSA’s virulence. More recent research in our lab has led to the identification of an enriched extract, 430D-F5, exhibiting increased potency. The fraction inhibits the accessory gene regulator (agr) pathway of S. aureus,
which is key to quorum sensing and thus toxin production in S. aureus2. Since this fraction targets a pathway non-essential for survival, a potential therapeutic derived from 430D-F5 would exert far less pressure for the development of resistance.
Ronnie Festok Exploring the Dynamic Chemistry of Emergent Peptide Templates Ronnie Festok, Emory University; Yushi Bai, PhD, Emory University; David G. Lynn, PhD, Emory University Chemical evolution is a type of natural selection that functions on a molecular level. This is largely a function of templation: small organic units polymerized into increasingly complex biopolymers, eventually developing the ability to template hereditary information across generations. Evolution on a molecular level thus begins to generate a diversified and complex library of molecules over time through responses to external stimuli. Modeling such systems is possible through the design of Dynamic Chemical Networks (DCNs) in which a library of molecules in solution compete and respond to selective pressures. Previous research has been conducted in which an NH2-NFF-CHO template emerging from mixed phase environments directed the nucleation of chain-length specific peptide polymers. This project seeks to extend that work to generate both chain-length- and sequence-specific oligomers that have the potential to mutualistically interact with DNA/RNA templates by diversifying the NH2-NFF-CHO system with Ac-RFF-CHO monomers. Furthermore, we sought to synthesize and modify a collagen-like derivative that allows us to analyze how the 3-dimensional orientation of the peptide backbone influences the amplification of a generated template. Doing so might help us better understand the mechanisms underlying chemical evolution while also exploring the mutualistic peptide/nucleic acid relationship.
Joseph Fonseca Use of biomaterial cues to enhance cardiac biological pacemaker function Joseph Fonseca, Morehouse College; David Wolfson, BS, Emory University; Hee Cheol Cho, PhD, Emory University Abstract not available.
Somnath Ganapa Actin Filaments' Role in Human Respiratory Syncytial Virus Assembly by Cryo-EM Somnath Ganapa, The College of New Jersey; Dylan Price-Wittenauer, Oxford College of Emory University; Zunlong Ke, PhD candidate, Georgia Institute of Technology; Elizabeth R. Wright, PhD, Division of Pediatric Infectious Diseases, Emory University School of Medicine Human respiratory syncytial virus (hRSV) is the leading cause of lower respiratory tract disease in young children, immunocompromised adults, and the elderly. The World Health Organization estimated that globally there are 64 million annual cases of hRSV infection leading to 160,000 deaths. Currently, no vaccines exist and palivizumab is the only medication available to infants diagnosed with a predisposition to infection, underscoring the need to better understand hRSV to combat its infection. hRSV is an enveloped virus with a negative-sense RNA genome that utilizes host cellular machinery to replicate. Actin filaments are part of the cellular cytoskeleton and are suggested to play a role in the hRSV assembly process through cellular trafficking. However, the molecular mechanism of how hRSV assembly depends on the actin filaments remains unclear. By studying the role of actin in hRSV assembly, we hope to facilitate new antiviral drug design. We have used cryo-electron microscopy (cryo-EM), immuno-fluorescent microscopy, and actin-destabilizing chemicals to study how hRSV utilizes the cell’s cytoskeleton during infection. Viral titration of hRSV infected cells treated with an actin-destabilizing compound suggests hRSV may require actin filaments for viral assembly. In addition, we have explored methods of manually and automatically segmenting the cytoskeleton filaments with Amira and EMAN2.2 software.
Jeff Gao Recurrent Neural Network Model for Fly Behavioral Transitions Jeff Gao and Gordon Berman, PhD, Emory University Background: The behavioral transitions of fruit flies (Drosophila melanogaster) exhibits long time scales, far beyond what would be predicted from a Markovian model, indicating that there are internal states that carry memory over long time scales. We sought to fit a generative model to the behavioral transition data of fruit flies and prune the model to find the essential parameters. Methods: A generative recurrent neural network long short-term memory model was fitted on fly behavioral transition data from recordings of 59 flies. The generative model was used to generate sequences of behavioral transitions. To tune the parameters of the number of hidden layers and nodes of the model and select for the optimal model with the best fit and fewest parameters, Akaike Information criterion (AIC) and Bayesian Information criterion (BIC) were used. Once the optimal model was selected, lasso regularization (L1 regularization) was used to prune the model. Results: A generative long short-term memory model was successfully fitted on the fly behavioral transition data. The optimal model selected by Akaike Information criterion (AIC) was a 2 layer model with 30 nodes in each hidden layer. The optimal model selected by Bayesian Information criterion (BIC) was a 2 layer model with 10 node in each hidden layer. A L1 regularization multiplier of 10-4 was selected based on the log-likelihood and L1 norm of the models. Conclusions: Long short-term memory models were able to fit the fly behavioral transition data. Behavior dynamics can be understood through these models.
Julia Gensheimer Role of Glucocorticoid Signaling in CD8+ T Cell Function Julia Gensheimer, Emory University; William H. Hudson, PhD, Emory University; Rafi Ahmed, PhD, Emory University Abstract not available.
Camille Hanes Investigating the Potential of CaMKII to Rescue Lethality in dNab2 Homozygous Mutant Drosophila melanogaster Camille Hanes, Program in Biochemistry, Cellular and Molecular Biology, The College of Wooster, Wooster, OH; Binta Jalloh, Chris Rounds, Ken Moberg, Department of Cell Biology, Emory University, Atlanta, GA; Seth Kelly, Program in Biochemistry, Cellular and Molecular Biology, The College of Wooster, Wooster, OH Intellectual disability (ID) is a neurodevelopmental disorder characterized by impaired intellectual functioning. Affecting around 1-3% of the population, patients with ID exhibit a lower IQ, as well as the inability to demonstrate adaptive behavior. Although intellectual disabilities vary in causative factors, loss of the ZC3H14 gene in humans has been linked to a nonsyndromic form of autosomal recessive intellectual disability. ZC3H14 encodes the Cys 3His (CCCH) tandem zinc finger polyadenosine RNA binding protein. The post-transcriptional role of ZC3H14 involves polyadenylation of the mRNA transcript and regulation of poly(A) tail length. However, the target mRNAs of ZC3H14, as well as the overall role of ZC3H14 in gene expression remain unknown. Preliminary data suggests that ZC3H14 may bind to CaMKII mRNA and regulate its translation. Interestingly, CaMKII is a kinase prevalent in the brain and is critical for calcium signaling and learning and memory. To further study the function of ZC3H14 and its potential interaction with CaMKII, a Drosophila melanogaster model has been established using the ZC3H14 Drosophila ortholog, dNab2. Neuronal levels of CaMKII and dNab2 protein were quantified and rescue experiments were performed. The elevated CaMKII level in flies lacking dNab2 suggests an interaction does exist between these two genes and further supports the model that ZC3H14 regulates levels of CaMKII protein. Further studies investigating this potential interaction will offer insight into the underlying cellular and molecular mechanisms of human ID.
Chad Hicks Developing the Molecular Constituents for Templated-Assembly of N,O-Acetal-Linked Polymers Chad Hicks, Emory University; Dr. David Lynn, PhD, Emory University Amyloid-beta (16-22) and its congeners have been shown to self-assemble into nanotubes that catalyze template-directed imine-linked polymerization on their surface. These and other types of condensation reactions catalyzed by self-assembled nanotubes could lead to the formation of less reversible, more complex supramolecular structures with novel catalytic repertoires. N,O-acetal condensation chemistry on the nanotube surface has yet to be tested. In this project, I develop a synthetic strategy and make progress towards constructing 4-hydroxy-3aminomethylbenzaldehyde and 6-hydroxy-5-aminomethylnaphthaldehyde. These molecules will be combined with the HLVFFAE amyloid-beta (16-22) nanotube congener to initiate templatedassembly of N,O-acetal-linked polymers on the nanotube surface.
Mengtong Hu Investigating the role of LCMT-1 in Hematopoiesis by Using a Conditional Knockout Mouse Model Mengtong Hu, Jessie Tran, Dainel Bujnowski, Ruhika Prasad, Zhengqi Wang, Ph.D.; Kevin Bunting, Ph.D.; David C. Pallas, PhD. Emory University School of Medicine Abstract not available.
Soyon Hwang Visualizing Brain Oscillations During Natural Interactions in Prairie Voles Soyon Hwang, Elizabeth Ann Amadei, Robert Liu Abstract not available.
Alexa Iannitelli Identification of Neural Circuitry Associated with Psychosocial Stress-Induced Cocaine Seeking in Rats Alexa F. Iannitelli, Daniel F. Manvich, David Weinshenker Stress contributes to relapse in abstinent addicts, and paradigms in which rodents “reinstate� cocaine seeking are used to simulate how relapse operates in humans. However, the physical and pharmacological stressors used in these paradigms poorly reflect the psychosocial stressors that precipitate relapse in humans. To more accurately depict the social pressures that are associated with cocaine relapse in humans, we developed social defeat stress-induced reinstatement in rats. To identify brain regions contributing to relapse-like behavior, c-Fos immunohistochemistry
(IHC) was utilized to compare the neural activation of brain regions following cocaine reinstatement in stressed and non-stressed animals. The analyzed regions include the paraventricular nucleus of the hypothalamus (PVN), the shell and core regions of the nucleus a ccumbens (NAC), the dorsomedial and ventrolateral sections of the ventromedial nucleus of the hypothalamus (VMHdm and VMHvl), the basolateral amygdala (BLA), and the central nucleus of the amygdala (CeA). The PVN and amygdala were chosen due to their recognized roles in the stress response system, the NAC was assessed for its role in the reward circuitry of the brain, and the VMHdm and VMHvl were chosen due to their respective roles in predator and aggressive conspecific stress. Our analysis revealed robust c-Fos activation in the PVN of defeated animals as compared to the control group. Additionally, the NAC core and VMHvl of defeated animals showed a trend towards higher activation. These data suggest that psychosocial stress-induced reinstatement recruits neural circuitry distinct from that previously identified for physical and pharmacological stressors in models of relapse.
Connor Innes Genes associated with phase variation from translucent to opaque colonies in Acinetobacter baumannii Connor Innes & Philip Rather, PhD, Emory University Acinetobacter baumannii is a widespread and highly resistant nosocomial pathogen that needs alternative approaches toward treatment. Recent observations and preliminary data of opaque and translucent phases of A. baumannii show the translucent phase is less virulent and more susceptible to defenses than the opaque variant. In this study, we sought to identify genes that are involved in the T to O switch. A. baumannii was mutagenized through transposon mutagenesis and screened for mutants that decreased translucent to opaque switching. Transposon insertions were mapped from selected mutants by partially digesting chromosomal DNA and cloning the transposon-associated resistance marker along with flanking chromosomal DNA. Complementation testing was then performed to confirm gene’s role in conversion. Our first mutant to be identified was MarTc Non-Switching 1 (MarTc NS1). MarTc NS1 has significantly decreased switching frequencies with a 164 and 8,708-fold decrease in switching at 24 and 48 hrs respectively. Through mapping of MarTc NS1, we found that the ribB gene contained an insert that we hypothesize is disrupting metabolic processes involved in the T to O switch. Complementation testing further supported this notion with a 155-fold increase in frequencies when ribB was restored in MarTc NS1. Further experimentation will test other proposed mechanisms and identify additional mutant strains. By analyzing which genes have a role in the T to O switch, we gain further insight into the regulatory mechanisms associated with phase conversion and can utilize this knowledge to develop new therapies to treat A. baumannii.
Daniel Jacobs Characterizing Human CPCs Daniel Jacobs, Emory University; Adrianna Mallett, Druid Hills High School; Michael E. Davis, PhD, & Joshua Maxwell, PhD, Emory University Abstract not available.
Jaewon Jeong Targeting Neuroinflammatory Signaling Pathway to Block the Epileptogenic Effect of EarlyLife Seizures Jaewon Jeong, Emory University; Jacob White1, B.A., Emory University; and Sookyong Koh M.D., Ph.D. Emory University Abstract not available.
Kaleena Jesson Long Term Vascular Regeneration After Traumatic Brain Injury Myles R. McCrary, MD/PhD candidate, James Y. Zhang, MD/PhD, Ling Wei, MD, and Shan Ping Yu, MD, PhD, Emory University Abstract not available.
Xinyi Jiang Effects of liquid extensional properties on the formation of giant soap films Xinyi Jiang, Stephen Frezier, and Justin C. Burton Huge bubbles have always captured the imagination of adults and children alike. Huge bubble solutions usually include soap as a surfactant and polymers as an additive. A polymer is a large molecule, composed of many repeated subunits and thus is able to change bubble formation behavior in a soap solution. We performed experiments on a range of different molecular weights of one type of polymer with various concentrations. We investigated the extensional properties, film lifetime and drainage rate of soap solutions and compared the results with the bubbles ability to form and be stable and quantify the extensional properties. The experiments so far have shown that the optimal bubble solutions exhibit a property of stable and similar length rapture length.
Mengtian Jin Big Data & Data Interface For Nursing Research Mengtian Jin, Emory University; Andi Plotsky, MSPH, Emory University; Roy L. Simpson, DNP, RN, DPNAP, FAAN, FACMI; Vicki Hertzberg, PhD Electronic healthcare records and data sets have been collected by medical institutions for many years, but have rarely been used for Nursing research purposes. Now there is enough data that could be used for Nursing research that would affect policy. One of the problems is that there is a lack of data exploration tools in the Nursing field. However, students and researchers need tools to start their research, develop hypotheses or help their studies. Our project used different software (mainly Oracle SQL, Tableau, Microsoft Access) to develop an easy-to-use data interface based on de-identified records pulled from the Emory electronic healthcare database. The main issues we dealt with were query response time, interface flexibility, and data security. With these issues solved, the data interface will allow the user to do fast searches, visualize data and get related data based on the use cases.
Joohee Kang Effects of Device-Guided Slow Breathing on Hemodynamics in Pre-Hypertensive PostTraumatic Stress Disorder Patients Joohee Kang, Ida Fonkoue Ph.D, 1Renal Division, Department of Medicine, Emory University School of Medicine and Research Service Line, Department of Veterans Affairs; Ryan M. Downey Ph.D, 1Renal Division, Department of Medicine, Emory University School of Medicine; Dana R. DaCosta B.S., and Jeanie Park M.D., Renal Division, Department of Medicine, Emory University School of Medicine and Research Service Line, Department of Veterans Affairs Patients who have post-traumatic stress disorder (PTSD) are at increased risk for developing hypertension and cardiovascular disease. Patients with PTSD have higher resting heart rate (HR) and blood pressure (BP) and decreased heart rate variability (HRV), suggesting a state of sympathetic nervous system hyperactivity. Prior studies have shown that device-guided slow breathing (DGB) may lower BP and SNS activity in hypertensive patients. We hypothesized that DGB will improve BP and SNS activity in PTSD patients. We recruited 21 veterans with PTSD and 13 controls; all study participants had prehypertension (mean BP, 125±2/80±2 mmHg). Participants were monitored with continuous EKG and beat-to-beat arterial blood pressure monitoring at rest and during 10 minutes of DGB using the RESPeRATE device or the sham device. From baseline to the end of 10 minutes of DGB in PTSD patients, there was a significant reduction in systolic blood pressure (SBP, -11±3 mmHg, p=0.001), diastolic blood pressure (DBP, -6.5±2 mmHg, p=0.003), and mean arterial pressure (MAP, -8±2 mmHg, p=0.001). We observed a significant reduction in SBP (-7±3 mmHg, p=0.029) in control patients with DGB use, and a trend towards reduced DBP and MAP. The sham device use in PTSD patients showed a reduction in SBP, DBP, and MAP. There was no significant change in HR (p=0.093), RMSSD (p=0.143), and pNN50 (p=0.203) with DGB or with sham device. If DGB has long-term beneficial effects on SNS activity and regulation in PTSD, it could represent a novel therapeutic intervention to improve autonomic physiology in PTSD patients.
Saumya Karne Cocaine sensitization in mice lacking β-arrestin2 in D1- or D2-containing cells Saumya Latha Karne, Kirsten A. Porter-Stransky, Canaan Jerome, and David Weinshenker Drug abuse is a major health issue costing in excess of $700 billion in the US annually according to the National Institute on Drug Abuse. Addictive drugs, such as cocaine, increase dopamine transmission in the nucleus accumbens (NAc), causing dopamine to bind and activate dopamine receptors, which are G protein-coupled receptors (GPCRs). β-arrestin2 (βarr2) is a protein found in most neurons that desensitizes and internalizes GPCRs, including dopamine receptors, and can also initiate G protein-independent signaling pathways. There are two classes of dopamine receptors, D1 and D2, which are highly expressed in non-overlapping populations of NAc neurons. The goal of this study was to examine the impact of selective βarr2 deletion from D1 or D2 neurons on cocaine sensitization, a form of drug-induced plasticity that may impact cocaine’s addictive properties. The results indicated that mice lacking βarr2 in D1-containing cells did not show any difference in cocaine sensitization in comparison with wildtype mice. However, mice lacking βarr2 in D2-containing cells did not sensitize to cocaine, indicating that βarr2 in D2containing cells is important for this form of cocaine-induced plasticity.
Benjamin Kasavan Local Glass Transition Temperature Tg(z) Profile in Polystyrene next to Polybutadiene With and Without Plasticization Effects Benjamin L. Kasavan, Roman R. Baglay, Connie B. Roth, PhD, Emory University. Glassy polystyrene (PS) is often toughened by incorporating rubbery polybutadiene (PB) within it. This resulting material, which is commonly known as high impact polystyrene (HIPS) has the ability to withstand stronger impacts and to deform more before breaking than pure PS. The glass transition temperature (Tg) is the temperature at which a material transitions from a liquid rubber to a solid glass. This Tg within a material varies as the distance from the interface changes. Small molecule additives such as plasticizers influence how the Tg varies near an interface. We present the measurements of the local glass transition temperature Tg(z) of PS next to PB rubber, expanding our previous data to a polymer with a much lower Tg value (PB Tgbulk = -96 ºC). After accounting for a small molecule additive present in the commercial PB sample that would otherwise migrate over to the PS domain causing plasticization, we find the Tg(z) profile in PS next to PB to be consistent with our previous results. We also demonstrate that these broad and asymmetric experimentally observed Tg(z) profiles are not caused by the migration of short low molecular weight chains across the interface by comparing samples made with two different poly(n-butyl methacrylate) (PnBMA) molecular weights.
Umar Khan Finer Time Resolutions Hold More Information in Motor Cortical Spiking Umar Khan, Emory University; Ilya Nemenman, PhD, Emory University; Sam Sober, PhD, Emory University It has been shown that millisecond-scale spike timing can often encode more information than spike rate in sensory systems. Recent studies have shown the same with some motor processes, notably in songbirds. Here, we have investigated the same question with center-out reaching motions in Rhesus Macaques. We have calculated the mutual information between the two discretized variables of neuron spiking responses and monkey reaching behavior. Our results indicate that the mutual information between these two variables increases at finer time resolutions.
Spencer King Pendrin Gene Ablation Activates the Thiazide-Sensitive Cotransporter Spencer King, Derek T. Pham, and Susan M. Wall, M.D., Renal Division, Department of Medicine Emory University Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of intercalated cells of the connecting tubule and cortical collecting duct, where it modulates NaCl absorption. The thiazide-sensitive NaCl cotransporter, NCC, mediates NaCl absorption in the distal convoluted tubule. Under basal conditions, pendrin gene ablation (i.e. pendrin KO mice) produces a small reduction in blood pressure, although a profound natriuresis, chloriuresis, and fall in blood pressure are observed in mice lacking both NCC and pendrin. As such, NCC and pendrin compensate for each other’s absence. While NCC gene ablation increases pendrin abundance, the effect of pendrin gene ablation on NCC is unknown. This study determined if pendrin deletion stimulates NCC and determines if it occurs by reducing serum K +. Pendrin KO and their WT littermates received a NaCl-restricted (0.5 meq/day NaCl or 0.07% NaCl), K +restricted (0.04 meq/day K+ or 0.1% K+) diet. Total NCC, active NCC (pSer124-NCC), and the α, ß, and Γ subunits of ENaC were quantified in kidney lysates from mice in each group by immunoblotting. In the Na+, Cl-, and K+-restricted mice, pendrin gene ablation reduced serum K+ from 3.9±0.28 to 3.1±.33 meq/L (P < 0.05) and reduced the abundance of all 3 ENaC subunits. In contrast, pendrin gene ablation doubled active NCC (pSer124-NCC, P < 0.05), although total NCC was unchanged. We conclude that eliminating pendrin activates NCC, which is a likely compensatory mechanism that limits the natriuresis, chloriuresis and the fall in blood pressure in these mutant mice.
Carli Kovel Modulating the Catalytic Activity of First-Row Transition Metal Complexes with Redox-Active Ligands that Incorporate Hydrogen Bonding Interactions Carli Kovel; Sophie Cemaj; Jessica Elinburg; Omar Villanueva, PhD, Georgia Gwinnett College; John Bacsa, Phd, Emory University; Savita Sharma, PhD, Emory University; and Cora E. MacBeth, PhD, Emory University The development of novel and efficient methods to selectively oxidize organic molecules is an important goal for many fields of science. One of the most widely employed methods for the oxidation of feedstock molecules to industrial compounds is via transition metal catalysis. The majority of the metal catalysts used in these methods utilize second- and third-row transition metals, which are both detrimental to the environment and economically costly. In nature, organic substrate oxidation reactions are observed in various enzymes that use first-row transition metal ions, which are more abundant and environmentally friendly. For example, catechol oxidase is an enzyme that catalyzes the aerobic oxidation of catechols to quinones and uses copper(II) in its active site. The research presented herein focuses on the development of highly-efficient first-row transition metal catalysts capable of oxidizing organic substrates under aerobic conditions. Our approach lies in the use of redox-active ligand scaffolds to enhance the catalytic reactivity of first-row transition metal catalysts with oxygen. This presentation will describe the development, synthesis, characterization and catalytic reactivity of cobalt(II), copper(II), and zinc(II) complexes supported by a redox-active ligand with hydrogen-bonding donor groups.
Kaela Kuitchoua The effects of maternal care on the structural development of brain reward circuits Kaela Kuitchoua; Elyse Morin; Mar M. Sanchez, PhD, Emory University; Martin Styner, PhD, University of North Carolina, Chapel Hill Child maltreatment is a public health concern because people who were maltreated as children are more susceptible to psychiatric illnesses, including depression, post-traumatic stress disorder and drug addiction, as well as social impairments. Underlying mechanisms are not well known, but they potentially involve alterations in brain development, including in structural and functional connectivity between regions and networks associated with emotional regulation and reward/motivation. Because testing these hypotheses during human development is very difficult, I am using an established rhesus monkey model of infant maltreatment. This study will compare regions associated with reward and emotional regulation between maltreated rhesus monkeys and controls to examine how maternal care affects the structural development of reward/motivation and emotional regulation systems, including the prefrontal cortex, amygdala and hippocampus. This study will also determine relationships between the structural development of these regions and prosocial, affiliative, behavior in the animals by examining whether structural volume at 18 months of age (juvenile period) predicts prosocial behavior at the same age.
Jayanth Kumar Effect of chemotherapy drugs on murine breast cancer, lung cancer, and immune cells Jayanth Kumar Dr. Ramireddy Bommireddy, PhD, Emory University Luis E. Muñoz, Graduate Student, Emory University Dr. Periasamy Selvaraj, PhD, Emory University Lung cancer is the leading cause of cancer death worldwide, and breast cancer is second leading cause of cancer death in women. Major types of breast cancer include hormone receptor positive (ER+PR+), HER2 positive, and the triple negative breast cancer. The target of our research is triple negative breast cancer (TNBC). The triple negative means the three most common types of receptors known to fuel breast cancer growth–estrogen, progesterone, and the HER-2/neu– are not expressed in the cancer cells. This subtype of cancer is highly heterogeneous and target antigens vary from patient to patient making it very difficult to treat. Surgery, radiotherapy and chemotherapy are the common treatment options for cancer patients. Chemotherapy is a cancer treatment that utilizes anti-cancer drugs as part of the treatment. However, recurrence is common in the majority of cancer patients due to the ability of cancer cells to develop resistance to the treatment and the side effects of such treatments on patients’ ability to produce immune cells such as white blood cells, making one prone to disease. My research is to investigate chemotherapy drugs that are effective in inhibiting 4T1, a murine TNBC, LL2, a lung cancer, and their effect on the body’s immune cells. Our results demonstrate that Cisplatin, Gemcitabine, and 5-FU are effective in inhibiting 4T1 TNBC, LL2 growth and immune cell activation. These studies warrant further in-vivo studies for treating TNBC and lung cancer patients.
Aliana Lawrence Lymphatic cell functional response and morphogenesis under flow in an abmormal lymphatic environment Aliana Lawrence, Spelman College; Joshua Hooks, Georgia Institute of Technology; J. Brandon Dixon, PhD, Georgia Institute of Technology Lymphatic malformations are the non-malignant overgrowth of lymphatic vessels that present at birth. Remediation efforts and management of the disease have proven to be futile because there is a lack of viable models that can accurately represent the presentation of the disease. Commonly, management of the disease can involve surgery, a form of sclerotherapy, and most recently, the administration of small molecule drugs. Without an in-depth understanding of the presentation of lymphatic malformations at the molecular level, there is an insistent need to understand and replicate in vivo frameworks. Previous studies have led to the understanding of lymphatic endothelial cell adaptation and organization to flow in collagen gels and on monolayers. The proposed approach will be to determine whether lymphatic endothelial cells and lymphatic muscle cells grown in collagen gels will exhibit a considerable reaction and interact together under flow. This reaction will be measured by the exchange of calcium between adjacent cells. In addition, the goal will be to see the overall lymphatic functional response and morphogenesis under flow in this abnormal lymphatic environment. Also, without considering reaction to flow, we will determine the level of expression of 4 proteins in the samples: eNOS, SMA, VEGFR-3, and MHC. Gaining a clearer understanding of the chemical and physical
behaviors of lymphatic cells could potentially lead to the engineering of tissue platforms that capture the complexity of in vivo behaviors leading to more targeted remediation.
Wei-Hsuan Lee Investigating transgenerational genetic interactions between an RNA binding protein, dNab2, and planar cell polarity components in Drosophila melanogaster Wei-Hsuan Lee, undergraduate, Emory University; Edwin Corgiat & Christopher Rounds, PhD candidates, Emory University; Kenneth Moberg PhD, Emory University. Intellectual disability consists of a cluster of developmental disorders characterized by defects in adaptive functioning and an IQ of less than 70. Mutations in a ubiquitously expressed polyadenosine RNA binding protein (RBP), ZC3H14, have been linked to a form of monogenic non-syndromic autosomal recessive intellectual disability. Understanding post-transcriptional mechanisms underlying the functions of this RBP can help elucidate common cell biological defects underlying intellectual disabilities as a whole, and possibly forge a path forward for broadly applicable diagnostic and therapeutic approaches. Highly evolutionarily conserved, ZC3H14 has a functionally conserved ortholog, dNab2, in Drosophila melanogaster. Dominant modifier screens show genetic interactions between dNab2 and multiple components of the planar cell polarity (PCP) pathway. The PCP pathway is important for tissue organization in development of vertebrates and invertebrates. Various PCP components, such as Disheveled, can rescue dNab2 overexpression phenotypes and interestingly show a transgenerational rescue effect with progeny lacking the PCP allele. Here we show that this transgenerational rescue effect is shared by multiple PCP components with functional and neuroanatomical consequences. We also validate the function of YFP-tagged dNab2 as a tool that can be utilized to further probe this effect.
Kathy Li Functions of KLF5 in Chemosensitivity of Mesenchymal Triple Negative Breast Cancer Cells Kathy Li, Jamie King, Jin-Tang Dong, PhD, Emory University. The transcription factor KLF5 has been suggested to play a major role in the transition of cancer cells from an epithelial to mesenchymal status (EMT), which promotes tumor invasion, metastasis and, chemoresistance. The acetylation status of KLF5 is important in controlling its function as a tumor promoter, repressor or EMT inducer. Another molecule, TTK kinase, is involved in controlling mitotic checkpoints. Mesenchymal stem like cell lines express the least amount of KLF5 and overexpress TTK. We hypothesize that restoration of wild-type or acetylation deficient KLF5 will make TNBCs more sensitive to chemotherapy, while restoring acetylation mimic will maintain similar sensitivity to parental cells. We also hypothesize that in conjunction with TTK inhibition, the effects will be even greater. Western blotting, PCR, and viability assays will be utilized to explore the effects of KLF5 restoration and TTK inhibition on cell sensitivity to chemotherapy treatment. Understanding the factors that contribute to TNBC sensitivity to chemotherapeutic treatments can give great insight into alternate standards for
clinical breast cancer treatment, particularly for these cancers lacking the receptors that are normally targeted.
Valerie Linck A mitochondrial defect in the ion channel, VDAC3, alters ENaC activity via ROS Valerie A Linck, Li Zou, Yu-Jia Zai, Laura I Galarza-Paez, Linda Li, Tiffany L Thai, He-Ping Ma, and Douglas C Eaton It has been suggested that voltage-dependent anion channels (VDACs) control the release of superoxide (O2-) from mitochondria. We have shown that reactive oxygen species (ROS) like O2- and hydrogen peroxide (H2O2) stimulate epithelial sodium channels (ENaC) in sodiumtransporting epithelial tissue including cortical collecting duct (CCD) principal cells. Therefore, VDACs could regulate ENaC by modulating cytosolic ROS levels. Our patch-clamp data show a significant difference in ENaC single-channel activity between wild-type (WT) and VDAC3 knockout (KO) mice on high salt diet for two weeks, but not on normal diet. Western blots show that a high salt diet significantly increases the expression of cleaved Îł-ENaC in VDAC3 KO mice only. Furthermore, systolic blood pressure was significantly increased in VDAC3 KO mice but not in WT mice on a high salt diet. Electron microscopy shows a significant morphological change occurs in CCD cells of VDAC3 KO mice on a high salt diet compared to WT mice, possibly caused by superoxide overload in the mitochondria. These data suggest that deletion of VDAC3 sensitizes ENaC to high salt challenge and promotes salt-sensitive hypertension. This is presumably due to ROS release in close proximity to ENaC in the apical membrane since mitochondria are concentrated below the apical membrane. Mitochondrial superoxide would be trapped in the mitochondria of VDAC3 KO mice, but can be degraded by mitochondrial superoxide dismutase to produce H2O2, which can freely move across the outer mitochondrial membrane into the cytosol. Therefore, the activation of ENaC could be a direct effect of H2O2.
Eva Liu Low temperature high-resolution spectroscopy of optically active quantum dots in atomically thin materials Meiran (Eva) Liu, Emory University; Xiaotong Chen, Emory University; Xin Lu, PhD, Emory University; Sudipta Dubey, PhD, Emory University; Qiang Yao, Emory University; Ajit Srivastava, PhD, Emory University Recently discovered quantum dots in atomically thin materials, such as transition metal Dichalcogenides, are promising candidates for a wide range of applications ranging from chemical sensing to optical devices. Despite the excitement generated in the community since their discovery, a thorough understanding and characterization of their optical properties, crucial to fully harness their potential, is still lacking. In this project, we undertook experiments to understand the intrinsic optical properties of quantum dots with high spectral-resolution optical spectroscopy. In particular, we performed light suppression and MOSFET gate voltage tuning to characterize and control the quantum dots found on monolayer tungsten diselenide sample. Our
next step is resonance fluorescence spectroscopy at cryogenic temperatures, which will give us information about the intrinsic emission line width and fine structure of the quantum dots. The findings of this study adds to the fundamental understanding of these novel quantum dots and the ability to better control their properties.
Solana Liu Acute Effects of D2 Receptor Agonist Sumanirole on Microglia Polarization after Ischemic Stroke Solana Liu Stroke, the second leading cause of death worldwide, affects 800,000 Americans each year and occurs on average once every 40 seconds. After early stages of ischemic injury, a protracted inflammatory reaction occurs within a few hours which includes the activation of microglia, which play induce the inflammatory response within minutes. Activated microglia polarize on a spectrum between the M1 proinflammatory and M2 alternatively activated forms and the resultant form is critical to functional recovery. Modulation of molecular and cellular mechanisms after stroke fosters functional recovery after stroke and a recent study suggests that dopamine may serve as a modulator of microglia function during neuroinflammation. In vivo activation of D2R, dopamine receptor D2, inhibits astrogliosis and neuroinflammation after stroke, which suggests the therapeutic potential of utilizing D2 agonists to protection against ischemia-induced neuroinflammation. This project explores the acute effects of utilizing a highly selective D2 receptor agonist Sumanirole on microglia polarization at varying timepoints after ischemia.
Haleigh Machost Synthesis and Purification of Disubstitution Triazoles via C-H Activation Haleigh Machost, Annette Neuman Triazoles have many medicinal applications, including their antitubercular, anticancer, and antifungal properties. Most commonly, disubstituted 1,2,3-triazoles are formed through cycloaddition; however, a mixture of regioisomers is formed, resulting in half of the synthesized material having different or no biological activity. Additionally, a distinct synthetic method is often required to produce one of the reagents. This is because the starting material containing what will become carbon number five in the completed triazole needs a specific attached group. In an effort to solve these issues, the formation of a disubstituted 1,2,3-triazole from a starting monosubstituted 1,2,3-traizole is accomplished through C-H activation. Using a palladium catalytic cycle, the 1,5- disubstituted isomer of a 1,2,3-triazole is believed to be produced, and a library of triazoles can be made through introducing various boronic acids into the catalytic cycle. This library can be enlarged through beginning the synthetic process with different aromatic azides. The disubstituted triazoles are then purified by alumina column chromatography. This is followed by recrystallization from a mixture of ethanol and water to
separate the starting monosubstituted triazole from the disubstituted product. The success of this new synthetic method is supported by mass spectrometry data.
Caroline Maguire IL-1 Signaling Mediates Costimulation Independent Rejection Caroline Maguire, Dave Mathews, and Andrew Adams, MD, PhD, Emory University In 2016, roughly 33,000 people received life-saving solid organ transplantation. The primary barrier to successful transplantation is immune-mediated rejection, specifically T cell mediated graft injury. Potent but non-specific small-molecule drugs called calcineurin inhibitors (CNIs) have been the backbone of transplant immunosuppression for the past 30 years. CNIs effectively suppress early “acute� rejection. However, due to its non-specific mechanism of action, CNIs potentiate a number of unwanted side effects such as heart attack, stroke, diabetes and hypertension. Long-term outcomes have failed to improve in organ transplantation, in part, due to reliance on CNIs. In 2011, the first CNI alternative, belatacept, was approved for use in kidney transplantation. Belatacept is a CTLA4-Ig fusion protein, which specifically blocks CD28mediated T cell costimulation, and adoption of belatacept leads to improved long-term survival. However, a significant subset of patients experience early T cell mediated graft injury while on belatacept based immunosuppression. We hypothesize that a more highly differentiated, memory T cell subset is capable of dispensing with CD28 signaling, and mounting a rejection response by relying on alternative cytokine signaling through the IL-1 receptor. Our goal is to investigate the role of the IL-1R1 in a mouse model of costimulation independent rejection.
Alicia May Role of ERK1 Signaling Pathway in Regulating Sodium Excretion through Renal Sodium Chloride Co-transporter (NCC) Alicia May, University of Georgia; Xinxin Chen, MD, Emory University; Jia Xiao, MD, Emory University; Xiuyan Feng, MD/Phd, Emory University; Shan Chen, MD/Phd, Emory Univgersity; Hui Cai, MD, Emory University Background: Sodium chloride cotransporter (NCC) plays a key role in the regulation of blood pressure and electrolyte homeostasis. Our previous study has shown that NCC protein was increased when ERK1/2 knockdown in mDCT cells. Our preliminary studies showed that NCC was decreased in the inducible renal tubular specific ERK2 KO mice. These results suggest that the ERK1 and ERK2 modulate NCC differently. Thus, we hypothesized that ERK1 plays an important role in affecting renal sodium excretion through NCC. Methods: Cell culture, transfection, western blot analysis, and metabolic cage study. Results: To determine whether ERK1 involves in NCC regulation in vivo, we first did western blot analysis experiments. We found that NCC abundance was increased in renal tissues of ERK1 KO mice. We further investigated whether ERK1 affects NCC expression in Cos-7 cells transfected with both ERK1 siRNA and HA-NCC plasmid. We found that ERK1 knockdown increased NCC expression in vitro. To further investigate whether ERK1 affects the function of NCC, we did metabolic cage
study in ERK1 KO mice administrated with either control vehicle or HCTZ, a specific NCC inhibitor. We found that 8-h urinary sodium excretion in ERK1 KO mice was lower than that in WT mice. HCTZ treatment increased sodium excretion in both ERK1 KO and WT mice. ERK1 KO mice have more exaggerated response to HCTZ treatment compared to WT mice in urinary Na excretion. Conclusions: ERK1 signaling pathway plays inhibitory role in NCC function and NCC protein expression. Funding: VA Merit Award (HC).
Micaela McCall Acute and Chronic Deep Brain Stimulation Effect on Heart Rate Variability Micaela McCall, Andrea Crowell, Helen Mayberg Dysregulation in the autonomic nervous system’s balance between sympathetic and parasympathetic tone is associated with negative mental health outcomes such as major depressive disorder. Deep brain stimulation (DBS) of the subcallosal cingulate cortex (Brodmann area 25) is an experimental surgical treatment for treatment resistant depression (TRD). BA25 is associated with the neural circuitry of autonomic regulation. Depression is associated with low parasympathetic control of the heart, resulting in low heart rate variability (HRV-the naturally occurring variability in the time between heart beats). This study investigates the effect of DBS on parasympathetic control of the heart by measuring HRV in response to acute onset and offsets of stimulation as well as in response to chronic stimulation over time. Additionally, this study seeks to address the question of whether there is laterality in the neural circuits of parasympathetic control. Acute unilateral stimulation showed no differential effect of left vs right on HRV. Nor did acute bilateral stimulation show any consistent effect on HRV. Over time, HRV measured under resting conditions of chronic stimulation did not change at the group level. These results suggest that there is no direct effect of DBS on parasympathetic control of the heart. However within individuals, HRV is initially uncorrelated with depression symptom severity, but becomes correlated with depressive symptoms over time. This suggests that there is an interaction between HRV, stimulation, and symptoms that emerges over time and contributes to the process of becoming well through DBS.
Jennifer McGuire Exploring the Effects of Adsorbed Layers on the Glass Transition and Physical Aging Jennifer A. McGuire, Michael F. Thees, Connie B. Roth, PhD, Emory University Recently, Thees and Roth detected unusual physical aging in thin polystyrene films at ultra-high molecular weights (≥ 6,500 kg/mol) compared to high molecular weight (≤ 3,500 kg/mol) films. Our goal was to explain this behavior, and the irreversibly adsorbed layers observed by others in the literature presented a possible explanation. To test these layers as an explanation, we first verified an experimental procedure for growing adsorbed layers of different thicknesses. Upon confirming reasonable agreement with the literature, we studied the physical aging rate of films with known adsorbed layer thicknesses. We found adsorbed layer thickness to depend on the cleanliness of the substrate, with cleaner substrates resulting in thicker adsorbed layers. We also
saw no observable difference in physical aging rate in ultra-high molecular weight and high molecular weight polymers for varying adsorbed layer thicknesses, eliminating the presence of adsorbed layers as an explanation of the observed unusual physical aging.
Sanket Mehta Intracellular delivery of labeling probes using a novel microfluidic approach Sanket Mehta, Sam Raines, Anna Liu, Vikram Varadarajan, Todd Sulchek Abstract not available.
Hayley Moyer IL-6 Activates the Mineralocorticoid Receptor via the JAK2/STAT3 Pathway, Increasing Sodium Chloride Cotransporter Expression Hayley C. Moyer, Gillian G. Hecht, Otor Al-Khalili, Rickta Mallick, Douglas C. Eaton, Robert S. Hoover and Brandi M. Wynne Hypertension is an inflammatory disease that is a leading cause of death and disability worldwide and is characterized by increased sodium (Na +) reabsorption. The beneficial effect of mineralocorticoid receptor (MR) antagonists in reducing blood pressure suggests a role for the MR in hypertension. Interestingly, the MR ligand, aldosterone is not always increased; however, the pro-inflammatory cytokine, interleukin 6 (IL-6), is elevated in hypertensive individuals. Previously we have shown that IL-6 increases MR-dependent Na + uptake in vitro and increases expression of the sodium chloride cotransporter (NCC) in vivo. Cytokines produce intracellular effects through multiple pathways, including the JAK/STAT signaling pathways. This has also been previously linked to numerous inflammatory responses in the kidney; however, the specific JAK/STAT pathway combination that may mediate Na+ absorption remains unidentified. Additionally, no studies have shown that the IL-6/JAK/STAT pathway is important in cytokinemediated Na+ reabsorption. We hypothesize that the JAK2/STAT3 signaling pathway is involved in MR-mediated activation of NCC. Using a luciferase reporter assay, our data show that IL-6 increases mineralocorticoid response element (MRE) activity via the JAK2/STAT3 pathway in a cell model of distal convoluted tubule cells (mDCT15). Additionally, we show that IL-6 infusion increases the IL-6 receptor-dependent signaling molecule gp130, and phosphor(T53)NCC. Together, our data suggest a mechanism of IL-6 mediated NCC activation and JAK2/STAT3 activation of the MR in the distal nephron. These data demonstrate an alternative mechanism for increased distal nephron Na+ reabsorption in hypertension when aldosterone levels are not increased, but increased levels of cytokines are observed.
Judith Ogbue Does Maternal Singing Increase Attention Holding in the Fetus? Judith Ogbue and Jaleyah Walker Our study sought to explore the extent to which maternal singing promotes longer durations of attention-holding in the fetus. Fetal attention is known to be associated with decreased movement. If short periods of maternal singing are presented at varied times, then it may prevent fetal habituation and increase durations of attention. We monitored the duration of decreased movement in fetuses (n=3) within their third trimester of gestation. During the experiment, we monitored fetal movement across trials of varied rates of maternal singing. We performed a case analysis (within-subjects design) which measured the mean duration and range of sustained attention. Results showed that the hypothesis was partially supported. Future directions will address standardization of procedures, replication of the study, aggregation of multiple subjects, and postnatal follow-up.
Javier Omar Gamma-aminobutyric Acid (GABA) and Executive Function in Healthy Older Adults Javier Omar, Emory University; Keith M. McGregor, PhD, Center for Visual and Neurocognitive Rehabilitation; Joe R. Nocera, PhD, Center for Visual and Neurocognitive Rehabilitation; Lisa Krishnamurthy, PhD, Center for Visual and Neurocognitive Rehabilitation Gamma-aminobutyric acid (GABA), the brain’s primary inhibitory neurotransmitter, plays a crucial role in shaping and controlling cortical excitability. Current research implicates decreased cortical GABA levels with aging. This age-dependent reduction in GABA serves as a model for understanding the neurochemical foundation of cognitive decline. We aim to quantify GABA concentrations in both healthy younger and older individuals through the use of proton magnetic resonance spectroscopy (1H-MRS). In addition to quantification, we are interested in establishing the relationship between GABA levels and cognitive performance, specifically verbal fluency. Verbal fluency is an important aspect of language function and includes selective attention and inhibition, verbal working memory, and executive control of speech. We will assess verbal fluency using a battery of cognitive assessments including the Hopkins Verbal Learning Test, Delis-Kaplan Verbal Fluency Test, Controlled Oral Word Association Test, as well as working memory assessments (e.g. – digit span, reverse digit span). We hypothesize that participants with lower concentrations of GABA will demonstrate poorer verbal fluency function, as compared to participants with greater concentrations of GABA. Our findings will illuminate how GABA concentrations are involved in age-related cognitive decline, especially with regard to verbal fluency.
Eddy Ortega The Synthesis of (1S,3R,4R)-ethyl 1-((tert-butoxycarbonyl)amino)-3-fluoro-4hydroxycyclopentanecarboxylate From Hippuric Acid As A Precursor For PET/CT Scan Imaging Modalities In Cervical Cancer Patients Eddy Ortega, Srirama Murthy, Thomas Pickel, and Lanny S. Liebeskind Currently there is no definite imaging technique for staging prostate carcinoma. The current imaging modalities come with limitations. PET scans show some promise, but current radiotracers lead to high urinary excretion shortly after administration, which leads to low detection in scans. The development of a better radiotracer is needed, with little to no urinary excretion, for better evaluation of patients with prostate carcinoma. The F-18 amino acids developed to date have four shortcomings in their application to prostate imaging. (1) they have uptake in benign prostatic hyperplasia, which adversely affects discrimination between cancer and inflammation, (2) there are unexplained variations in undesired accumulation of radioactivity in the bladder of subjects, thus masking the detection of tumors in primary and loco-regional lymph nodes, (3) there are variations in washout of the radioactivity from tumors affecting the tumor signal background and (4) they have mixed amino transport system specificity. It has been determined that high LAT1 levels are associated with decreased overall in prostate cancer. Therefore there is a need is in a LAT (“L� large-neutral amino acid) specific 18F non-natural amino acid for use in prostate cancer that diminishes these four limitations. To overcome these issues difuorinated amino acids have been chosen as molecular targets in order to (1) use the higher F-content to disfavor the undesired partitioning of the radiotracer into the aqueous contents of the bladder, and (2) to provide an excellent substrate for 19F nucleophilic substitution.
Samuel Raines Microfluidic Delivery of Fluorescent Antibodies via Mechanoporation for Differentiation of Cancer Cell Lines and Immune Cells Sam Raines, Sanket Mehta, Anna Liu, Vikram Varadarajan, and Todd Sulchek Abstract not available.
Divyaansh Raj The Effect of IL-6 and CRP on the White Matter Tracts of Patients with MDD Divyaansh Raj, Emory University; Ki Sueng Choi, PhD, Emory University School of Medicine; Boadie Dunlop, MD, Emory University School of Medicine; Helen Mayberg, MD, Emory University School of Medicine Major Depressive Disorder (MDD) is common and highly disabling. Pathophysiological studies emphasize a role for specific brain regions organized in neural circuits with various treatments impacting and correcting regional and network dysfunction. Imaging has revolutionized the study of MDD with techniques enabling studies of network structure and function. Diffusion
methods using magnetic resonance imaging allows the more precise study of white matter tracts including various methods to measure white matter integrity and functional connectivity between regions. Inflammatory cytokines have been recently implicated as a putative etiological agent in some cases of MDD. This project will measure the relationship of inflammation, measured in the blood, with integrity of white matter in the brain, measured using diffusion MRI imaging. We will test the hypothesis that high c-reactive protein (CRP) and interleukin-6 (IL6) levels damage white matter as indexed by focal abnormalities in fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) in connections linking regions previously associated with MDD. Inflammatory markers and MRI scans previously acquired in MDD patients will be used to test this hypothesis.
Whitley Ramirez Development of First-Row Transition Metal Complexes for the Aerobic Oxidation of Catechols Whitley Ramirez; Omar Villanueva, PhD, Georgia Gwinnett College; Carli Kovel; Savita Sharma, PhD, Emory University; and Cora MacBeth, PhD, Emory University. The aerobic oxidation of organic substrates remains an important goal in chemistry for its relevance in a significant number of catalytic processes in industry and nature. In particular, the development of sustainable catalysts capable of using oxygen to oxidize organic compounds has received considerable attention due to its environmental and sustainability aspect. First-row transition metal complexes capable of promoting the activation of oxygen (a multi-electron process) has been relatively rare due to their one-electron reactivity limitation that differs them from those displayed by second- and third-row metal ions. Our approach to this challenge involves developing redox-active ligand scaffolds capable of promoting such reactivity at firstrow metal centers. Redox-active ligands have demonstrated to play critical roles in biological reactions involving multi-electron processes. For example, galactose oxidase is a copper oxidase that uses a copper(II)-tyrosyl radical and oxygen to aerobically oxidize primary alcohols. In this study, we have developed a dianionic redox-active ligand scaffold capable of stabilizing monometallic first-row transition metal complexes. This presentation will describe the development, spectroscopic and structural characterization, and catalytic reactivity towards catechols of cobalt(II), copper(II), and zinc(II) complexes supported by a dianionic bidentate redox-active ligand.
Sarah Renahan A study of reproductive capacity in galactose-1-phosphate uridylyltransferase (GALT)-null Sprague Dawley rats Sarah Renahan, Emory College, and Judith L. Fridovich-Keil, PhD, Dept. of Human Genetics, Emory University School of Medicine More than 80% of girls and women with classic galactosemia experience premature ovarian insufficiency. Here we conducted a pilot experiment testing the ability of young adult male and
female GALT-null rats to produce offspring. This work was part of our initial characterization of a new GALT-null rat model for classic galactosemia.
Samantha Rudin-Rush The Role of ATP7a in Drosophila Neural Development and Function Samantha Rudin-Rush, Undergraduate, Agnes Scott College; John Davis, Medical Student, Mercer Medical School; Avanti Gokhale, PhD, Emory University; Victor Faundez, PhD MD, Emory University; Cortnie Hartwig, PhD, Emory University & Agnes Scott College Metal homeostasis is an important factor in everyday biochemical processes of the human body. Genetic factors can disturb this balance. For example, Menkes disease is an X-linked inherited disorder that results in a copper deficiency. This disease is diagnosed at infancy and is fatal, with affected individuals having an average life span of three years. Menkes disease occurs from a mutation in the ATP7A gene that produces a dysfunctional copper transmembrane protein. ATP7A is expressed in all tissues except the liver. Copper plays a part in neurotransmission, a contributing factor to the neurodegeneration that characterizes Menkes disease. The goal of this study is to map the molecular mechanisms occurring in Menkes disease. Using a Drosophila neuromuscular junction (NMJ) assay, we observed a quantifiable effect on synapse morphology of ATP7A transgenic animals. Furthermore, we identified a novel interaction between ATP7a and the golgi related COG complex that regulates neurodevelopment. We have developed a high throughput screen to observe the effects of the ATP7A interactome on the fly eye as well as a protocol to measure the effects of protein changes and copper levels of animals with ATP7a deficiencies.
Daniel Salgueiro Kinetics of Rhodium(III)-Catalyzed Allylic C-H Amination of Disubstituted Olefins Daniel C. Salgueiro, Undergrad, Emory University; Simon B. Blakey, PhD, Emory University The formation of C-N bonds is a process that is relevant throughout different concentrations of organic chemistry. Performing these reactions catalytically could help chemists synthesize desired products, most notably bioactive molecules. Thus far, intermolecular C-H amination has only been shown to be possible on terminal olefins. This work seeks to expand upon previous work done in the Blakey group that has proven intermolecular C-H amination is possible on disubstituted olefins. Through modifications of both the olefin and the nucleophile, we aim to provide a definitive methodology for the formation of allylic C-N bonds on disubstituted olefins and, ultimately, intermolecular C-H functionalization in general. Additionally, we aim to gain insight on our reaction system through various kinetic experiments following the model of Donna Blackmond’s reaction progress kinetic analysis.
Simone Salter Dialysis Provider Knowlege of Change in the New Kidney Allocation System and the Transplant Process Simone Salter, University of Georgia; Mohua Basu, MPH, Kayla D Smith, BA, and Stephen Pastan, MD, Emory University School of Medicine; Laura Plantinga, PhD, Emory University School of Medicine, Rollins School of Public Health; Sumit Mohan, MD, MPH, Columbia University; Cam Escoffery, PhD, Rollins School of Public Health; Joyce Kim, BA, Emory University School of Medicine; Taylor Melanson, BA, Rollins School of Public Health; Rachel E Patzer, PhD, MPH, Emory University School of Medicine, Rollins School of Public Health In December 2014, the national kidney allocation system (KAS) changed, allowing end-stage renal disease patients to receive credit for placement on the kidney transplant waiting list from time of dialysis start instead of time of waitlisting. These changes were intended in part to benefit African American patients who have longer times on dialysis and lower access to transplant. However, for KAS to be effective, dialysis providers should be knowledgeable about these changes. This study aims to describe provider knowledge of KAS changes and to examine KAS knowledge differences by facility and provider characteristics. A 5-item scale (1 point for each correct item) was used to measure provider knowledge of KAS as part of a survey administered in September 2016 to 1,529 dialysis providers from U.S. facilities in the lowest national tertile for waitlisting. Survey data from 653 respondents were linked with 2014 United States Renal Data System data to obtain dialysis facility characteristics. Descriptive, t-test, and chi-square analyses were conducted using SAS 9.4 to explore differences in KAS knowledge by facility and provider characteristics. Results indicate provider knowledge of KAS was low overall (Mean: 2.38, SD: 1.43). Providers who were male (vs. female) (p=0.008), medical directors (vs. social workers, nurses, facility administrators, and other staff) (p <0.001), and providers from non-profit (vs. for-profit) facilities (p=0.04) had higher KAS knowledge. Providing KAS education to dialysis providers is important. These changes may benefit their ESRD patients, especially African Americans with longer times on dialysis, potentially leading to increased access to kidney transplantation.
Brycen Saunders Use of PLG Nanoparticles to Treat Neuroinflammation and Epilepsy Jacob White, BA Russell Sanchez, PhD Young Jin Jung, MD Sookyong Koh, MD/PhD Abstract not available.
Alec Shannon Behavioral and Neurochemical Outcomes of Restored Norepinephrine Synthesis in Noradrenergic Cells in a DOPA-Responsive Dystonic Mouse Model Alec Shannon; Christine Donsante, MS; Maria Briscione; Danielle McFarlane; Rong Fu, PhD; Anthony Downs; Kaitlyn Roman; H.A. Buz Jinnah, MD, PhD, Emory University; Ellen Hess, PhD, Emory University Dystonia is a neurological disorder that is clinically diagnosed in patients exhibiting involuntary twisting movements, uncontrollable muscle contractions and spasms, and dystonic tremor. Clinicians often use a patient’s response to levodopa administration to diagnose certain forms of generalized dystonia; patients who respond to low levels of levodopa treatment are considered to have a form of dystonia known as dopa-responsive dystonia (DRD). Individuals with DRD also exhibit significantly reduced dopamine concentration in the brain—a symptom of dystonia that the Hess-Jinnah lab has generated in a DRD knock-in mouse model by recapitulating the human tyrosine hydroxylase (TH) mutation. Although the TH mutation significantly reduces the synthesis of both dopamine and norepinephrine, it is assumed the lack of dopamine causes the dystonia. However, the role of norepinephrine, if any, in the pathogenesis of dystonia is unknown. The overall goal of this project is to explore the contribution of norepinephrine to the pathology of dystonia by rescuing TH expression in noradrenergic neurons, but not dopamine neurons, of DRD mice and characterizing the behavioral and neurochemical profile of this unique mouse model.
Preston Sheng Exploiting Drosophila to examine RNA exosome-linked disease Preston Sheng, Emory University; Derrick J. Morton, PhD, Emory University; Binta Jalloh, Emory University; Christopher Rounds, Emory University; Ken Moberg, PhD, Emory University; Anita H. Corbett, PhD, Emory University Many diseases begin as the result of small, single base mutations in the genome. Identifying these diseases can prove very challenging. One area of interest is the multi-protein RNA exosome complex, a complex that plays a crucial role in the degradation and processing of RNA. Mutations in multiple genes that encode RNA exosome subunits are linked to distinct disease. Interestingly, RNA exosome subunit EXOSC3 is linked to Pontocerebellar Hypoplasia Type 1b (PCH1b), a disease affecting the cerebellum and the pons, causing severe intellectual and motor defects. Those effected typically do not survive past childhood. My preliminary data show that we can assess RNA exosome function in a tissue specific manner in Drosophila. Knockdown of EXOSC3 (fly Rrp40) in all neurons (elav>Gal4), glial cells (repo>Gal4) and globally (actin>Gal4) is lethal in development. However, there have been no studies conducted yet to determine whether the Rrp40 subunit is required for maintenance. I will use the UAS-Gal4 system, as well as exploiting a temperature sensitive mutation, to determine the effect of Rrp40 knockdown in fully developed, mature flies. These studies will provide insight into the function of the RNA exosome in vivo and explore the functional consequences of defects in the RNA exosome linked to very distinct disease.
Anika Sinha Regulation of wzz2 Promoter Activity and Protein Levels at 25°C and 37°C in Pseudomonas aeruginosa Anika Sinha, Oxford College of Emory University; Ashley R. Cross, Emory Laney Graduate School, Microbiology and Molecular Genetics Program, Graduate Division of Biological and Biomedical Sciences; Joanna B. Goldberg, PhD, Emory University School of Medicine Understanding how virulence factors in pathogenic organisms are regulated is imperative to developing new and innovative treatment methods. Such is the case in Pseudomonas aeruginosa, an opportunistic pathogen that causes life-threatening infections in immunocompromised people. P. aeruginosa has a virulence factor located on the outer membrane called the O antigen (OAg). OAg is attached to the lipopolysaccharide and aids the bacterium in evading the host’s innate immune system defenses. Very long (VL) lengths of OAg are controlled by the chain length regulator Wzz2. Based on previous findings that OAg VL chain length decreases as temperature increases, it was hypothesized that cultures grown at 25ºC would have increased wzz2 promoter activity and Wzz2 protein amount compared to growth at 37ºC. Therefore, promoter activity of wzz2 and Wzz2 protein levels were investigated at different temperatures during the stationary phase of growth. The wzz2 promoter region was fused to a promoterless-lacZ and inserted into laboratory strain PAO1. PAO1 was then grown at 25ºC, environmental temperature, and 37ºC, host body temperature. Through the use of β-galactosidase assays, promoter activity was measured, and through the use of Western blots, the protein amount was visualized with specific antibodies to Wzz2. β-galactosidase assays determined that wzz2 promoter activity was increased at 37°C compared to 25°C. Western blot analysis determined that Wzz2 protein levels were unchanged at 37°C compared to 25°C. These results indicate that there are likely wzz2 posttranscriptional regulation mechanisms controlling VL OAg chain length in P. aeruginosa. Future experiments will further investigate these mechanisms.
Austin Slone Exercise Mediates Anesthetic Emergence and Recovery in Diabetic and Control Rats Austin Slone, Vanderbilt University; Christopher G Sinon, BS, Emory University; Amy Ottensmeyer, MD, Emory University; Matthias Kreuzer, PhD, Emory University; Dr. Machelle Pardue, PhD, Georgia Institute of Technology, Atlanta VA Medical Center; Dr. Paul García Concerns exist about conditions characterized by deficits in working memory and executive function following surgeries involving general anesthesia. While diabetes and post-operative cognitive impairments have not been shown to be directly correlated, one study found that those with diabetes—roughly 10% of the U.S. population —were much slower to perform memory tasks following cardiac surgery. Additionally, studies performed with a Type 1 Diabetes rat model have shown post-anesthesia impairments in learning and memory, but the current study is the first to address this issue in a Type 2 Diabetes rat model. The aim of this project is to determine if exercise preceding anesthesia exposure prevents a decline in cognitive performance through any number of potential “neuro-protective” mechanisms. Each rat underwent ten days of exercise or rest prior to a 2-hour exposure to isoflurane. Pre- and post-anesthesia Y-maze tests, a timed scoring of their anesthesia emergence hallmarks, and a one-hour scoring of post-anesthesia
behavior were also performed. Exercised rats displayed a significantly decreased amount of time required to notice a sticky dot placed on their front limbs following anesthesia, indicating faster recovery. Exercised rats also demonstrated more uniform, longer times in the enclosure following isoflurane compared to varied enclosure times in idle rats. Moving forward, we plan to analyze the data from the animals undergoing two-hour oxygen exposures, examine brain tissue from these animals to identify biochemical markers potentially responsible for the results, and perform cognitive testing at later time-points following anesthesia.
Houston Smith The Temperature at which CO is Liberated from Methanol Ice Houston Hartwell Smith, AJ Mesko, Sarah Ferguson, and Samuel Zinga, Department of Chemistry, Emory University; Stefanie N. Milam, NASA Goddard Space Flight Center; Susanna Widicus Weaver The objective of this experiment is to understand how icy grain chemistry can lead to the formation of amino acids and other prebiotic molecules in the interstellar medium. Icy grain chemistry is found in dense regions of interstellar space, such as star forming regions. The ices are mostly comprised of water, methanol, ammonia, and other small organic compounds. The laboratory synthesis of glycine from these small compounds under interstellar conditions would give great insight into how amino acids might be formed in space. In this experiment, we are using rotational spectroscopy to probe the gas-phase chemistry above the ice during processing. An ultra-high vacuum chamber was used to simulate space, and a small amount of methanol was introduced into the chamber and frozen out on a cold stage. Two different types of experiments were performed. The first was a thermal desorption experiment of pure methanol ice while the second used photoprocessing for a period of time followed by thermal desorption. The goal of the first experiment was to benchmark our experimental setup with known literature values, and the goal of the second experiment was to determine the temperature at which CO is liberated from the methanol ice.
Kiandra Smith Investigation of dNab2 Loss in D. Melanogaster Causing Changes in Sleep/ Circadian Rhythms Kiandra Smith, Binta Jalloh, Ken Moberg, Seth Kelly Like all plants and animals, the circadian clock is important regulatory system that allows D. melanogaster (fruit flies) to maintain cyclic changes that result in behavior and physiology. This system is controlled by two feedback loops that control transcription and translation to allow a 24-hour periodicity of gene expression. Recently, a knockdown (KD) of dNab2, a protein essential for locomotion and flight in fruit flies, has shown that Clock mRNA transcripts, which is necessary for circadian clock function, are up regulated in flies lacking dNab2. We hypothesize that the absence of Nab2 alters the expression of proteins involved within the circadian clock system, thus altering the circadian rhythms in Drosophila. Because the circadian
clock system is essential in all organisms, this study can potentially provide a better understanding on how dNab2 (ZC3H14 in humans) affects human locomotion and its affects on shift work.
Lindsey Sniffen The effect of high fat high fructose diet on peripheral immune cell trafficking into the brain Lindsey J Sniffen, Lori N Eidson, Mary K Herrick, Kathryn P MacPherson, MalĂş G Tansey Abstract not available.
Hanyao Sun Optimization of Sequential Grooming in Drosophila Hanyao Sun and Gordon Berman Animals engage in a variety of serial behaviors, such as communication, prey capture etc. One of the primary models of sequential behavior is reminiscent of how Drosophila melanogaster, or fruit fly, selects among competing behavioral choices. From video recording, while grooming, dusted flies follow a predictable pattern In this paper, the optimization of Drosophila’s sequential grooming is studied and whether or not the hierarchical architecture is optimal for the cost function in light of evolution will be further investigated. The result might have implication to how nervous systems implement serial execution.
Grace Swaim Acentrosomal microtubules contribute to collective cell migration Grace L. Swaim and Dorothy A. Lerit While the migration of healthy cells is important for normal development, invasive cell migration, or metastasis, is a hallmark of advanced cancer phenotypes and the leading cause of cancer deaths. In vitro studies suggest that the organization of a microtubule-organizing center (MTOC) near the leading edge is critical for directed cell migration in some cells, but mechanisms underlying MTOC organization are cell-type specific. While centrosomes serve as MTOCs in most eukaryotic cells, other cells organize their microtubules acentrosomally. The follicle cells of the Drosophila egg chamber are model post-mitotic epithelial cells that organize microtubules acentrosomally. During mid-oogenesis, a cohort of follicle cells undergoes an epithelial-to-mesenchymal transition to form a cluster of migratory cells referred to as the border cells. Border cells are an excellent model of invasive cell migration. During mid-oogenesis, border cells migrate past 15 germline-derived nurse cells to reach the nurse cell-to-oocyte border. Although microtubules are required for efficient border cell migration, mechanisms mediating the acentrosomal organization of these microtubules are poorly understood. In order to understand the underlying mechanisms of acentrosomal cell migration, we established an assay
to quantify cell migration efficiency in the context of an intact tissue. Using the Drosophila ovary as a model system, we show that border cells require several conserved regulators of microtubule assembly, such as centrosomin, for collective cell migration, despite the fact that these cells lack functional centrosomes. To determine whether acentrosomal microtubules mediate invasive cell migration, examining microtubule organization in our migration-deficient mutants will be an important next step.
Jordan Swanier Comparative Phytochemical Analysis of Citrullus ecirrhosus and Citrullus mucosospermus using HPLC and LC-MS Jordan S. Swanier, James T. Lyles, Cassandra L. Quave In 2014, over 120,000 acres of watermelon were grown in the United States, yielding 3.2 billion pounds of the crop. The domesticated watermelon, or Citrullus lanatus (Thunb.) Matsum. & Nakai, is a member of the Cucurbitaceae family with other squashes and melons. This research refers to the plant using the older synonym, C. mucosospermus, since accessions were originally described with this binomial. Collaborators from the USDA Plant Genetic Resources Conservation Unit observed varying degrees of insect herbivory of the leaves of two related Citrullus species: C. ecirrhosus and C. mucosospermus. Citrullus ecirrhosus is a wild desert perennial that is accustomed to growing in the arid climates of the Democratic Republic of Congo. Field observations showed that the leaves of this species exhibited insect-repellent properties. However, the leaves of C. mucosospermus were ravaged by insects. Understanding the differences in secondary metabolites for these species of Citrullus can reveal information about the anti-herbivory properties of the plants and assist in lowering the production costs of Citrullus crops by reducing the use of pesticides. This research analyzed the chemical fingerprints of C. ecirrhosus and C. mucosospermus using liquid chromatography-mass spectrometry (LC-MS) and observed that C. ecirrhosus possessed 98 unique secondary metabolites not present in C. mucosospermus.
Jaleyah Walker Does Maternal Singing Increase Attention Holding in the Fetus? Gloria Faboyede, MS, Judith Ogbue, Jaleyah Walker, and Eugene Emory, Ph. D., Emory University Our study sought to explore the extent to which maternal singing promotes longer durations of attention-holding in the fetus. Fetal attention is known to be associated with decreased movement. If short periods of maternal singing is presented at varied times, then it may prevent fetal habituation and increase durations of attention. We monitored the duration of decreased movement in fetuses (n=3) within their third trimester of gestation. During the experiment, we monitored fetal movement across trials of varied rates of maternal singing. We performed a case analysis (within-subjects design) which measured the mean duration and range of sustained attention. Results showed that the hypothesis was partially supported. Future directions will
address standardization of procedures, replication of the study, aggregation of multiple subjects, and postnatal follow-up.
Marshall Weber Pt(II) CNC Pincer Complex as Catalyst for Alkenyldiol Cyclization Marshall J. Weber, BS, Emory University; Frank E. McDonald, PhD, Emory University Some natural products have potential or known medical uses,but thecomplex structures of these compounds make their syntheses difficult. One such natural product is brevenal, which is a promising combatant todiseases such as cystic fibrosis and chronic obstructive pulmonary disease (COPD). Brevenal, along with other naturalproducts, contains multipleetherrings. My project centers on the cyclization of an alkenyldiol substrate using a platinum (II) CNC pincer catalyst, as shown in the figure below. Similar platinum pincer catalysts have already been used for oxacyclizations and carbocyclizations.The hypothesized procedure would involve only one catalytic stepto produce tetrahydropyran, whereas the current procedures for such a cyclization are stoichiometric and therefore create much waste, in addition to requiringa second step. If successful, this project could inform the synthesis of natural products includingbrevenal.
Shaniece Wilson Fluid Attenuated Inversion Recovery (FLAIR) Imaging Overestimates Lesion Extent in the Orbitofrontal cortex of Rhesus Macaques Shaniece A. Wilson, Lauren E. Murphy, & Jocelyne Bachevalier Ph.D In vivo neuroimaging techniques have recently been used to accurately quantify the extent of neuronal damage after neurotoxic lesions of the medial temporal lobe structures in non-human primates (Malkova et al., 2001; Nemanic et al., 2002). These neuroimaging procedures have several advantages for behavioral research in non-human primates. They provide a way to rapidly determine whether the neurotoxin has reached the targeted structure, whether there is spreading to adjacent neural structures or, conversely, whether there is sparing of brain tissue within the targeted area. However, while this is an attractive technique, MRI in-vivo imaging should be validated. Thus, the first aim of the current study is to assess the reliability and reproducibility of these techniques in estimating lesion extent of cortical areas in nonhuman primates. The study will compare estimation of lesion extent of orbitofrontal area 13 using neuroimaging tools with actual cell loss found during histological evaluation of brain tissue.
Linda Wu Investigation on the Effect of Different Organic Cover Crop Techniques on Soil Fertility and Microbial Diversity. Linda Wu and Sarah C. Fankhauser, PhD, Oxford College of Emory University The microbial community within a piece soil is essential to the fertility of soil and success of the crop. Many species of bacteria can play a supporting, mutualistic, parasitic, and even harmful roles in the life cycle of a crop, and specific farming practices can play a deciding factor in generating different microbial communities. Thus, the aim of this project is to further investigate the effects that different organic farming practices have on the microbial communities and how these communities in turn affect crop production. The first year of the project investigates how bacterial communities change with different cover crops techniques. Planting cover crops is a farm practice that involves the process of growing specific crops on a field to restore the soil and prepare for the next growing season. Cover cropping may include planting singular species or multiple species together and may vary depending on the cash crop that the cover crop is preparing the soil for. Using an experimental plot on the Oxford College Organic Farm, we will look at how different cover crop strategies change soil fertility and determine changes in microbial diversity through next generation sequencing. We will further determine how these different cover crop strategies impact a subsequent broccoli crop production. In subsequent years the specific bacteria that correlate with improved broccoli crop yield will be further investigated.
Sarah Ye A transgenic mouse model for studying spermatogenesis and genome instability Sarah Ye, Emory University; Kanchana Poompui, Emory Univerity; Anthony W.S. Chan, PhD, Emory University Many neurodegenerative inherited diseases such as Kennedy’s disease, spinocerebellar ataxias, and Huntington’s disease are caused by trinucleotide repeat (TNR) mutations in coding genes. Studies have reported a correlation between higher expansion rate though paternal transmission and meiosis which suggests genome instability during spermatogenesis plays a role in disease transmission. Although germline expansions in trinucleotide disorders are well documented, the expansion mechanism is unknown. A working model system will be needed in order to further study TNR disorders and genome instability during spermatogenesis. This study aims to create a transgenic mouse model with a spectrum of fluorescent tags that are expressed in specific sperm cell types in the testicles (“Testi-bow mice). These “testi-bow” mice allow sperm cells to be identified at a specific stage of development which can be isolated and sorted for molecular analysis to determine the genome instability in specific types of sperm cells. “Testi-bow” mice will be characterized based on their specific transgene expression pattern in the sperm cells, and will be central in subsequent studies investigating genome instability and TNR expansion.
Kara Ye End Stage Renal Disease and Hypertensive Patients Have Altered Pattern of Heart Rate Variability Responses to Graded Lower Body Negative Pressure Kara Ye and Ryan M. Downey, Ph.D, Renal Division, Department of Medicine, Emory University School of Medicine, Research Service Line, Department of Veterans Affairs Medical Center; Peizhou Liao, Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University; Dana R. DaCosta, B.S., Renal Division, Department of Medicine, Emory University School of Medicine, Research Service Line, Department of Veterans Affairs Medical Center; Jeanie Park, M.D., Renal Division, Department of Medicine, Emory University School of Medicine, Research Service Line, Department of Veterans Affairs Medical Center End stage renal disease (ESRD) patients have autonomic neuropathy that contributes to increased cardiovascular (CV) risk. The normal autonomic response to orthostatic stress is to increase sympathetic nervous system (SNS) and decrease parasympathetic nervous system (PNS) in order to maintain blood pressure. Prior studies have shown that healthy humans have decreases in heart rate variability (HRV) in response to increased orthostatic stress induced by graded lower body negative pressure (LBNP). We hypothesized that ESRD patients have lower HRV and higher blood pressure variability (BPV) at baseline, suggestive of increased SNS and decreased PNS activity. We further hypothesized that ESRD patients will have an inability to adjust SNS and PNS in response to increasing orthostatic stress. We measured continuous beat-to-beat blood pressure and ECG at baseline and during increasing doses of LBNP in 3 study groups: ESRD, hypertensive controls (HTN), and healthy controls (CON). HRV was quantified as NN interval and SDNN, RMSSD, and pNN50. BPV was measured as the standard deviation in systolic blood pressure (SDSAP), diastolic blood pressure (SDDAP), and mean arterial blood pressure (SDMAP). We observed that baseline SDNN, RMSSD, and pNN50 were significantly lower in both ESRD and HTN compared to CON. Whereas CON exhibited gradual decreases in pNN50 with increasing LBNP, pNN50 remained constant in ESRD and HTN, suggesting a failure to adjust PNS activity to the heart in response to increasing orthostatic stress. Failure to adjust autonomic activity in response to orthostatic stress in ESRD and HTN may contribute to increased CV risk.
Paul Young Characterization of Diguanylate Cyclase-containing Globin-Coupled Sensors Involved in Bacterial Biofilm Formation Paul G. Young, Shannon Rivera, Carmen Metzler, Eric D. Hoffer, PhD., Christine Dunham, PhD., and Emily E. Weinert, PhD. Diguanylate cyclase-containing globin-coupled sensors (DGC-GCSs) are oxygen-sensing proteins which catalyze conversion of two guanosine triphosphate (GTP) molecules into bis(3’5’)-cyclic dimeric guanosine monophosphate (c-di-GMP). The role of c-di-GMP as a second messenger in bacterial signal transduction has been recognized. Chief among its functions is mediating the transition from the motile planktonic lifestyle to the sessile lifestyle in bacteria. This transition is important in the formation of biofilms, which are aggregations of bacteria attached to surfaces in a bacteria-synthesized hydrated polymeric matrix. Increasing awareness
that chronic bacterial infections often involve antibiotic resistance-conferring biofilms makes understanding the biochemical mechanisms underpinning their formation pertinent to disease prevention and treatment. This work aims to better understand the roles of heme-pocket residues in the DGC-GCS proteins of Pectobacterium carotovorum carotovorum (PccGCS) and Bordetella pertussis (BpeGReg) in intra-protein oxygen signal transduction. Furthermore, as the structures of these proteins remain elusive, X-ray crystallography was performed on the BpeGReg globin domain (BpeGlobin). Finally, to elucidate the effect of globin-coupled sensor proteins on biofilm formation in vivo, Congo Red biofilm assays were performed in Shewenella sp. ANA3 (SANA3).
Huiying Zhu Application of Global Optimization to Image Registration Huiying Zhu, Emory University; Lars Ruthotto, Phd, Emory University; Manuela Manetta, Phd, Emory University Image Registration is a process of transforming an image into a given reference image to foster efficiency of analysis. It aims at finding geometric correspondence between the reference and template image including rotation and shifting. The method of finding the best transform is to find smallest difference between reference image and transformed template image. Mathematically, this is phrased as an optimization problem. Due to the non-convexity of the objective function, prior approach of transformations commonly employed local optimization. The transformation could generate undesirable local minima as results, limiting the accuracy of the registration. This project evaluates the applicability of double descent and color intermittent diffusion (DDNCID), a method of global optimization, for image registration. DDCID is an iterative method that alternates two steps; (i) locating a local minimum using optimization and (ii) escaping the basin of attraction using random perturbations. Direct application of DDCID is complicated due to the non-coercivity of the objective function in image registration. Therefore, a thrust of this project is extending DDCID by bound constraints. We use a barrier function to enforce the bound constraints. This project aims to apply global optimization with log barrier constraint to improve the accuracy of image registration. Further research could include the choice of default boundary constraint and application of the log barrier constraint and global optimization into other image registration models.
Ruomin Zhu Gravitational Waves from Charged Black Hole Binaries Ruomin Zhu and Thomas Osburn This project investigates how the dynamics of binary black hole systems are affected by electric charge. Black hole binaries are common astronomical systems that radiate gravitational waves. Recent gravitational wave observations from binary black hole mergers are revolutionizing astronomy through access to a spectrum of radiation (gravitational waves) independent of the electromagnetic spectrum (light). We consider systems where a neutral black hole orbits a more
massive black hole with electric charge. Such systems are described by Einstein’s theory of general relativity. Because one binary component is assumed to be more massive than the other, Einstein’s and Maxwell’s equations are simplified through an expansion in powers of the small mass-ratio. Separation of variables via spherical harmonic and Fourier decomposition is used to reduce the system of coupled PDEs to coupled ODEs. This system of coupled ODEs is solved numerically using code written in Python. From the numerical solutions we calculate the rate of radiative energy dissipation and analyze the effect of radiation reaction on the orbital dynamics. We observe that the orbital radius decreases until the neutral black hole plunges into the more massive charged black hole, and we quantify the effect of electric charge on these inspiral dynamics