Kate O'Toole

 Kate O'Toole

Kate O'Toole

  • Courses9
  • Reviews29

Biography

Emory University - Biology


Resume

  • 2012

    StageLearn

    Inc.

    Assumption College

    Developed case study materials for high school STEM curriculum.\n\nThe case \"My brain made me do it...\" explores modern neuroimaging techniques and looks at their use in legal proceedings. Students are also introduced to neuroanatomy and the relationship between brain regions and their primary functions.

    StageLearn

    Inc.

  • 2005

    Emory University

    UMass Boston

    Emory University

    Upper-division Neurobiology course with an enrollment of 60 students. I integrated small group work

    think-pair-share style discussion questions and iclicker questions into classroom lectures. I also developed and implemented a Process Oriented Guided Inquiry (POGIL) case to introduce neuroanatomy through self and peer instruction. By the end of the lesson students had generated a \"compass\" of anatomical direction terms and were able to write \"driving directions\" to describe the location of key structures in the brain. The final group project was an extended case study introducing mental illness through an investigation of the life of the painter Vincent VanGogh. Group members worked together to research a mental illness and generate a poster for round-robin style individual presentations.

    UMass Boston

    Emory University

    Atlanta

    GA

    Lecture Track Faculty in the Biology Department \n\nCourses taught include:\nBIOL 141: Foundations of Modern Biology I\nBIOL 240: Organismal Form and Function\nBIOL 336: Human Physiology\n\nSpecial Seminars:\nIDS290: Bodies in Space: Dance & Proprioception

    Lecturer

    Atlanta

    GA

    Thesis Advisor: Andrew Jenkins

    Ph.D.\nFunctional and structural subdomains of the intracellular loop domain of the GABA(A) receptor α1 subunit\n\n\"My research experience resides at the intersection of Biology

    Chemistry

    and Physics. I proposed a novel role for the intracellular loop domain (ILD) in the GABA(A)R α1 subunit and sought to fill a critical knowledge gap in our understanding of the structure and function of this region of the protein. I conducted a systematic site-directed mutagenesis charge switch scan

    changing basic residues to glutamate and acidic residues to lysine

    in order to assay the role that individual ILD residues play in controlling channel function. Through careful characterization of these mutants using macroscopic and single channel voltage-clamp recording techniques

    I have shown that residues within discrete subdomains of the α1 ILD control channel gating

    desensitization

    and open probability. I have also shown that ILD residues affect ion permeation as seen by changes in relative reversal potential and single channel conductance. Taken together

    my results have established an important role for the GABA(A)R α1 ILD in controlling the architecture and hence function of this ion channel.\"

    Ph.D. in Neuroscience

    Emory University

    Ph.D.

    Thesis Advisor: Andrew Jenkins

    Ph.D.\n“Properties of the M3-M4 Intracellular Loop of the GABA(A) receptor revealed through mutagenesis”\n\nNIH T32 Predoctoral Institutional Training Grant

    Division Scholar

    Neuroscience

    Graduates in Neuroscience

    Graduate Student Council

  • 2003

    Northern Kentucky University

    Center for Science Education

    Emory University

    Honors Thesis Advisor: Patrick Schultheis

    Ph.D.\nWestern Blot Analysis of a putative P-type ATPase Mg2+ transporter

    Northern Kentucky University

    Teaching Fellow

    PRISM fellowship: NSF GK12 Grant\nPaired with High School teacher to design and implement Problem Based Learning cases. \nAP and Honors Chemistry at Grady High School

    Atlanta

    GA.\n\nFull cases and materials are published online at CASES Online: http://www.cse.emory.edu/cases/\n\n\"Table Town\" introduces the periodic table through a discovery of elemental properties.\nMr. Element has just moved to Table Town where there are very specific rules about where he can live. Will he like his new neighbors? Will he find the best place to live?\n\nThe \"Case of the Jacked Up Grill\" introduces oxidation and reduction chemistry with an inquiry based lab activity.\nLeon and Stanley bought grills for a great price from Pookie. But when Leon's teeth turn blue can they use their knowledge of Chemistry to determine what happened?\n\n\"Kate’s Conundrum\" uses a comic strip to introduce the biochemistry of proteins while reviewing inter- and intra- molecular forces. Final group presentations encourage students to be creative and use a comic strip

    skit

    song or rap to share their findings with the class.\nCan Kate figure out how to complete her thesis project on ion channels by learning about intermolecular forces? Can you help her figure out which amino acids are charged using your understanding of pKa values?\n\nEllis K

    Goins C

    Obeidin R

    O’Toole K. 2011. Troubled Waters. \nObeidin R

    O’Toole K

    Ellis K

    and Goins C. 2011. Something in the Air. \nO’Toole K and Obeidin R. 2011. Case of the Jacked Up Grill. \nFaircloth R and O’Toole K. 2010. Table Town. \nO’Toole K and Obeidin R. 2010. Avogadro’s Americano. \nO’Toole K and Obeidin R. 2010. Kate’s Conundrum.

    Center for Science Education

    Emory University

    Teaching Assistant

    Ronald Calabrese

    Ph.D.\t\nCourse: IBS 514 Cellular Neuroscience

    Emory University

    Nicole Minor

    Ph.D.; BIO 352L Genetics Lab\nLarry Giesmann

    Ph.D.; BIO 151L General Biology Lab

    \nJerome Langguth

    Ph.D.; HNR 101 Introductory Philosophy

    Northern Kentucky University

    Adjunct Professor

    Neuroscience capstone class for biology majors with an enrollment of 16 students. During lecture

    I am incorporating videos

    popular news articles

    primary literature

    case studies

    and in-class activities for better student engagement and understanding of the material. Within the lab

    I am using an inquiry based approach where students must propose a testable hypothesis

    then collect data and summarize their findings by writing an abstract to practice real world research and communication skills. This semester I introduced a new lab to the curriculum using Backyard Brains recording units for electrophysiology using the cockroach leg

    Assumption College

    Tufts University

    Boston

    MA

    Fellow in the TEACRS program supported by NIH funds to pursue career development in biomedical research and undergraduate science education.\n\nResearch adviser: Jamie Maguire

    Ph.D.\nStudying changes in excitability within the peritumoral region which lead to enhanced seizure susceptibility in animal models of Glioblastoma Multiforme

    Postdoctoral Associate

  • 2001

    BS

    Summa Cum Laude

    University Honors Scholar

    Most Outstanding Graduate: Biological Sciences

    Regents Scholar

    Biological Sciences

    Chemistry

    Tri Beta: Biological Honor Society

    Alpha Chi Honor Society

    NCAA Division II Volleyball

    Northern Kentucky University

  • Department of Biology | Emory University

    Department of Biology | Emory University

    CASES Online: Creating Active Student Engagement in the Sciences

    CASES Online is a collection of inquiry-based lessons to engage K-12 and undergraduate students in exploring the science behind real-world problems. Through CASES

    you can transform your students into motivated investigators

    self-directed and life-long learners

    critical thinkers and keen problem solvers. Our cases are grounded in Problem-Based Learning (PBL)

    Investigative Case-Based Learning (ICBL)

    and related student-centered pedagogies.

    Immunohistochemistry

    Tissue Culture

    Immunocytochemistry

    Molecular Biology

    Neuroscience

    Aseptic Technique

    Cell Culture

    Animal Models

    PCR

    Mutagenesis

    Scientific Writing

    Electrophysiology

    Western Blotting

    Data Analysis

    Discrete M3-M4 intracellular loop subdomains control specific aspects of γ-aminobutyric acid type A receptor function

    Andrew Jenkins

    The GABA type A receptor (GABA(A)R) is a member of the pentameric ligand gated ion channel (pLGIC) family that mediates ionotropic neurotransmission. Residues in the intracellular loop domain (ILD) have recently been shown to define part of the ion permeation pathway in several closely related members of the pentameric ligand gated ion channel family. In this study

    we investigated the role the ILD of the GABA(A)R α1 subunit plays in channel function. Deletion of the α1 ILD resulted in a significant increase in GABA EC(50) and maximal current amplitude

    suggesting that the ILD must be intact for proper receptor function. To test this hypothesis

    we conducted a mutagenic screen of all amino acids harboring ionizable side chains within this domain to investigate the contribution of individual charged residues to ion permeation. Using macroscopic and single channel voltage-clamp recording techniques

    we found that mutations within a subdomain of the α1 ILD near M3 altered GABA apparent affinity; interestingly

    α1(K312E) exhibited reduced partial agonist efficacy. We introduced point mutations near M4

    including α1(K383E) and α1(K384E)

    that enhanced receptor desensitization. Mutation of 5 charged residues within a 39-residue span contiguous with M4 reduced relative anion permeability of the channel and may represent a weak intracellular selectivity filter. Within this subdomain

    the α1(K378E) mutation induced a significant reduction in single channel conductance

    consistent with our hypothesis that the GABA(A)R α1 ILD contributes directly to the permeation pathway.

    Discrete M3-M4 intracellular loop subdomains control specific aspects of γ-aminobutyric acid type A receptor function

    David J. A. Wyllie

    Stephen F. Traynelis

    James P. Snyder

    C. Justin Lee

    Phuong Le

    Matthew R. Livesey

    Kevin Erreger

    Elyse Katz

    Matthew T. Geballe

    Philip E. Chen

    Journal of Physiology

    Modulation of glycine potency in rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes.

    Gary Shull

    Tamera Hagen

    Patrick Schultheis

    Biochem Biophys Res Commun.

    Characterization of the P5 subfamily of P-type transport ATPases in mice.

    Andrew Hooper

    Stress is the most commonly reported precipitating factor for seizures. The proconvulsant actions of stress hormones are thought to mediate the effects of stress on seizure susceptibility. Interestingly

    epileptic patients have increased basal levels of stress hormones

    including corticotropin-releasing hormone (CRH) and corticosterone

    which are further increased following seizures. Given the proconvulsant actions of stress hormones

    we proposed that seizure-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis may contribute to future seizure susceptibility. Consistent with this hypothesis

    our data demonstrate that pharmacological induction of seizures in mice with kainic acid or pilocarpine increases circulating levels of the stress hormone

    corticosterone

    and exogenous corticosterone administration is sufficient to increase seizure susceptibility. However

    the mechanism(s) whereby seizures activate the HPA axis remain unknown. Here we demonstrate that seizure-induced activation of the HPA axis involves compromised GABAergic control of CRH neurons

    which govern HPA axis function. Following seizure activity

    there is a collapse of the chloride gradient due to changes in NKCC1 and KCC2 expression

    resulting in reduced amplitude of sIPSPs and even depolarizing effects of GABA on CRH neurons. Seizure-induced activation of the HPA axis results in future seizure susceptibility which can be blocked by treatment with an NKCC1 inhibitor

    bumetanide

    or blocking the CRH signaling with Antalarmin. These data suggest that compromised GABAergic control of CRH neurons following an initial seizure event may cause hyperexcitability of the HPA axis and increase future seizure susceptibility.

    Seizure-induced disinhibition of the HPA axis increases seizure susceptibility

    Andrew Jenkins

    Jason Derry

    Paul Garcia

    Jim Richardson

    Anesthesiology

    A conserved tyrosine in the beta2 subunit M4 segment is a determinant of gamma-aminobutyric acid type A receptor sensitivity to propofol.

    Andrew Jenkins

    The GABA type A receptor (GABA(A)R) is expressed ubiquitously throughout the brain and is a target for many therapeutic agents

    including general anesthetics and benzodiazepines

    which enhance receptor function by increasing the open probability (P(o)) of the ion channel. It is commonplace for in vitro studies of receptor pharmacological characteristics to use negative membrane holding potentials to mimic the resting potential of neurons and symmetrical chloride to eliminate Goldman rectification

    which results in chloride flow in the opposite direction

    compared with in vivo conditions. This critical difference is usually overlooked because the GABA(A)R has been reported to behave as an ohmic pore

    but our results show that the current-voltage relationship is nonlinear with respect to P(o). Specifically

    we found that currents were outwardly rectifying at low P(o) and linear at high P(o). We confirmed the correlation between P(o) and rectification with a partial agonist

    piperidine-4-sulfonic acid

    and a gating-impaired mutation

    α1(L277A); both exhibited enhanced outward rectification. Furthermore

    this correlation was independent of Goldman rectification and persisted under altered chloride gradient conditions

    which suggests that rectification is linked to the direction of chloride flux. Finally

    our results showed that the degree of potentiation by general anesthetics (etomidate

    propofol

    and isoflurane) was greater at negative membrane potentials. Traditional in vitro experiments thus overestimate the action of positive allosteric modulators of the GABA(A)R. Our results show that the direction of the driving force on the permeant ion

    as well as P(o)

    must be considered together for a complete understanding of drug actions on ligand-gated ion channels.

    The Apparent Voltage Dependence of GABAA Receptor Activation and Modulation Is Inversely Related to Channel Open Probability

    Kate

    O'Toole

    Tufts University

141

1.5(1)

BIO 141

3.9(8)

BIO 141142

5(1)

BIOL 141

2.8(5)

BIOL 336

2.5(6)

BIO 336

2.5(2)

BIO 240

3.3(3)