The Training Core awards a number of mini-grants each year to our trainees for research projects. Below are summaries of the grants awarded since 2019, beginning with the most recent.
GURUGOWTHAM ULAGANATHAN
Exploring the Utility of Brain Spheres for Investigating Superfund Chemicals – November 2023
An in vitro induced pluripotent stem cell (iPSC) model – Brain Spheres, will be piloted to study the effects of chemical co-exposures on developmental neurotoxicity. The Brain Spheres model harnesses the tractability of iPSCs to recreate the system’s intricate 3D architecture while also recapitulating its extended developmental processes. This initiative aligns with the U.S. EPA’s goal of reducing reliance on vertebrate animals in toxicological research. Moreover, the Brain Spheres model will be the first 3D brain model used to study toxic exposures as part of the Duke Superfund Research Center. Guru Ulaganathan (PhD student, Murphy lab) will use this as a platform to investigate how chemicals and their mixtures modify the neural framework, with an emphasis on uncovering the underlying mechanisms behind observed perturbations.
DILLON KING
Conformational Changes in mtDNA Compaction Associated with mtDNA Damage – October 2021
Understanding how mtDNA damage is recognized and the signaling mechanisms that lead to repair or removal of damaged mtDNA is crucial to understanding how environmental chemicals that target the mitochondria influence both human and environmental health. The protein TFAM serves two purposes, to bind to and compact mtDNA into nucleoids and to initiate transcription of the mitochondrial genome. We hypothesize that mtDNA damage will result in alterations in the ability for mtDNA to form nucleoids around TFAM. In this project, Dillon King (PhD student, Meyer lab) will visualize the role of TFAM and conformational changes in the mtDNA nucleoid following DNA damage using Atomic Force Microscopy (AFM). The focus on the impact of DNA damage on specifically the mitochondrial genome directly falls in line with Project 3 of the Duke SRP.
CATHERINE WISE
Analysis of PBDEs in Canine Placental Tissues: Pet Dogs as a Model for Diseases of Developmental Origin – August 2021
Early life exposures to endocrine disrupting chemicals such as polybrominated diphenyl ethers (PBDEs) can disrupt crucial developmental processes that lead to chronic health issues later in life. Gestation is a particularly critical window for development and the placenta is increasingly recognized as a key player in mediating fetal exposures. Previous human studies have shown that PBDEs accumulate in the placenta in a sex- and tissue-specific manner. Pet dogs offer a unique opportunity to serve as a sentinel species for human environmental health studies because they share our environment, have similar genomes and diseases with similar clinical and biological features. Dr. Catherine Wise (Post doc, Stapleton lab) will demonstrate if pet dogs can act as a sentinel species to evaluate real-world environmental exposures in placental tissues.
PRABHA RANASINGHE
The role of the gut microbiota in mediating polycyclic aromatic hydrocarbon (PAH) toxicity in developing zebrafish: A missing link in PAH-mediated organismal toxicity – August 2021
The gut microbiome can shape a host by interacting with physiological processes such as neurodevelopment, metabolism, and immune response. Emerging studies indicate the need to better understand the role of microbiota as a target of xenobiotics and as a mediator of toxic effects by altering the toxicokinetic and/or toxicodynamic of environmental chemicals. However, the role that gut microbiota plays in mediating xenobiotic toxicity is not well understood. Dr. Prabha Ranasinghe (Post doc, Di Giulio lab) will conduct fundamental dose response studies to investigate the mechanisms by which host-associated microbiota influence the toxicokinetic/toxicodynamic of xenobiotics. She will focus on benzo(a)pyrene (BaP) as a contaminant of interest, and compare neurobehavioral toxicity in fish reared with and without a commensal microbiome.
SAMANTHA MURPHY
Evaluating trace element concentrations in sediment, water and Fundulus heteroclitus from Elizabeth River sites – August 2021
The overarching goal of this project is to determine trace element levels (i.e. lead, cadmium, arsenic, mercury, selenium, vanadium, zinc, copper, and manganese) in the water, sediment, and Fundulus heteroclitus (Atlantic killifish) in specific tributaries and sites in the Elizabeth River, Virginia. Samantha Murphy (PhD student, Jayasundara lab) will examine physiological responses, including potential evolved modifications to multiple trace elements in estuaries, which can improve our understanding of how site-specific exposure to metals can affect killifish on an organismal level as well as an eco-evolutionary level. To this end, killifish in the ER provide a unique study system to examine evolutionary adaptions to trace elements.
LINDSAY JASPERSE
Later life bioenergetic consequences of embryonic PAH exposure and increased temperature in subpopulations of Atlantic killifish from the Elizabeth River – January 2021
Subpopulations of Atlantic killifish (Fundulus heteroclitus) reside in the Elizabeth River (ER) and have evolved to survive in the most polluted sites along the river by developing resistance to PAHs. While developmental effects of embryonic exposure to PAHs are relatively well-established, less is understood about the later life consequences of early life exposure to PAHs in killifish. Dr. Lindsay Jasperse (Post doc, Di Giulio lab) will: (1) Determine metabolic rates of juvenile Atlantic killifish from different ER subpopulations following early life exposure to Elizabeth River sediment extract (ERSE) and increased temperature; (2) Assess the thermal kinetics of metabolic rates in juvenile Atlantic killifish from different ER subpopulations following early life exposure to ERSE; and (3) Measure heart and brain-specific mitochondrial function in juvenile Atlantic killifish.
ZADE HOLLOWAY
A novel visual assay for behavioral toxicology in zebrafish – November 2020
The use of zebrafish as a model to explore developmental toxicants and their interaction with the nervous system is a prominent theme in Duke SRP research. To date though, there are a limited number of behavioral analyses to assess visual function in these vertebras. Incorporation of a novel visual assay into the neurobehavioral toxicity core will allow further exploration of the pharmacological and neurotoxicological analysis of this model species. The aims of this project are two-fold: Dr. Zade Holloway (Postdoc, Levin lab) will (1) characterize behavioral function in zebrafish utilizing a novel method for assessing visual systems and (2) assess sensitivity of assay to behavioral disruption by known developmental neurotoxicant cadmium.
ANDREW HAWKEY
Mixture Effects of Cadmium and Benzo[a]Pyrene on neurobehavioral function in young zebrafish – November 2020
Ongoing research has shown the value of zebrafish as a model for the identification of toxins, teratogens and mechanisms of action. Zebrafish of varying ages are used in this capacity in the neurobehavioral toxicity core (NBT), and on projects 1, 2, and 4. The aims of this project are two-fold: Dr. Andrew Hawkey (Postdoc, Levin lab) will (1) validate neurobehavioral tests for juvenile zebrafish (e.g. 30-40 days post-fertilization) and (2) compare the neurobehavioral phenotypes of the fish exposed to cadmium, benzo[a]pyrene, or mixtures during embryonic development. The proposed research will advance a new line of research in the area of developmental exposures to toxicant mixtures and their lasting effects on nervous system function, and will broaden the tools available for examining the resulting neurobehavioral effects.
PAIGE VARNER
Sequencing the genome of Pseudomonas putida G7 harboring the naphthalene-degrading plasmid NAH7 for the purpose of promoting bioremediation of PAHs – September 2020
Paige Varner (PhD student, Gunsch lab) aims to sequence the genome of Pseudomonas putida G7 (G7) which harbors the naphthalene-degrading plasmid NAH7. Because this plasmid is well-characterized, it has been widely used to study bioremediation of polycyclic aromatic hydrocarbons (PAHs). Particularly this plasmid is an ideal candidate for genetic bioaugmentation (inserting relvant genes into the environment) because it is self-transmissible and well-characterized. This will allow for a deeper understanding of plasmid transfer for the purpose of bioremediation of PAHs. This knowledge will advance the goals of Project 5 by maximizing the PAH degradation in sediments. Additionally, this project will allow collaboration between Project 5 of the Duke SRP and the Duke Center for Genomic and Computational Biology.
AXEL BERKY
Toxic Trace Metals and their Health Implications on Public Health in Madre de Dios, Peru – February 2020
Axel Berky (PhD student, Pan lab) will assess the health effects of mixed trace metal exposures in a Peruvian population where other co-exposures are limited. This allows for a more robust assessment relating toxic trace metals to health outcomes. The specific aims are: 1) evaluate mixed metal exposures in Madre de Dios, Peru where mercury exposure has already been demonstrated to be highly pervasive; 2) utilize cross-sectional exposure, along with in-depth survey and detailed health data to quantify the effect of mixed metal exposure on cardiovascular and kidney health and 3) implement different statistical methods to identify a model that most accurately fits mixed exposures. This will allow us to more accurately assess mixed exposures and begin to link exposures to health outcomes, while adjusting for important covariates.
DANIEL RAUDABAUGH
Direct and Indirect Effects of Polycyclic Aromatic Hydrocarbons on Host-fungal partnerships and their potnetial to be leveraged for bio-remediation – February 2020
The importance of fungi as key drivers of aquatic ecosystem functions and their symbiotic relationships to host plants has been extensively researched. Plants have been known to uptake legacy and emerging pollutants, including polycyclic aromatic hydrocarbons (PAHs), via root uptake and subsequent translocation and through their stomata via atmospheric deposition. Unfortunately no research has been conducted to understand how these pollutants affect root-associated and endophytic fungi. To address this deficiency, Dr. Daniel Raudabaugh (Postdoc, Gunsch lab) will: 1) root-associated and endophytic fungi will be isolated from Phragmites australis (common reed) and Spartina alterniflora (salt marsh cordgrass) roots, and 2) culture-independent analyses will be completed to elucidate changes in fungal root-associated diversity and phylogenetic structure.
BEVERLY DESOUZA
Comparing the mutagenic potentials of PAH-containing samples that have been bioaugmented by bacterial strains with PAH-degrading capability – February 2020
Project 5 of the Duke Superfund Research Center aims to develop bioaugmentation strategies that employ bacteria and fungi to degrade environmental PAHs. Bioaugmentation offers the promise of removal of PAHs from contaminated sites without the environmental disruption and cost associated with currently used remediation methods such as dredging and capping. A potential drawback to bioremediation, however, is that microorganisms can create toxic byproducts in the degradation process. Beverly deSouza (Master’s student, Gunsch lab) will compare the mutagenic potentials of PAH-containing samples that have been bioaugmented with 3 bacterial strains isolated from the former Republic Creosoting site in the Elizabeth River, VA, with that of untreated controls.
KATHLEEN HERSHBERGER
Investigating potential mechanisms of later-life effects of a developmental exposure to arsenic using a multi-omics approach – January 2020
Arsenic is a well-established environmental toxicant that contributes to the pathogenesis of a number of diseases including cardiomyopathy, neuropathy, and cancers. Mitochondria biogenesis and reprogramming occur during early development and may be a period of heightened vulnerability to mitochondrial toxicants, including arsenic. However, understanding the long-term effects of exposure to arsenic during early development is prohibitively difficult to study in long-term epidemiological studies. The Meyer lab (Project 3) exposes C. elegans to arsenic in early development and follow the animals into adulthood. In this project, Dr. Kathleen Hershberger (Postdoc, Meyer lab) will determine potential mechanisms of later-life effects of a developmental exposure to arsenic using a multi-omics approach.
ZADE HOLLOWAY
Neurodevelopmental effects of vitamin E in embryonic zebrafish exposed to benzo[a]pyrene – February 2019
Analysis of effects on organisms and the environment from benzo[a]pyrene (BaP) exposure is a prominent theme in Duke SRP research, and advances in therapeutic treatments would greatly enhance our understanding and progress in this field. To date, vitamin E has not been explored as a therapeutic agent on embryonic development in the presence of this potent neurotoxin. Dr. Zade Holloway’s (Postdoc, Levin lab) project will benefit Projects 1, 3, and 4 of the Duke SRP by adding valuable data to what is known about the mechanisms of developmental neurotoxicants and their effects on early life exposure. This work will further our understanding of how antioxidants and other vitamin supplements may help protect organisms exposed to PAHs, and lastly provide us with pilot data that may be highly applicable to cases of exposure in humans.