Dr Ingo Greger University positionGroup leader Dr Ingo Greger is pleased to consider applications from prospective PhD students. InstitutesMedical Research Council Laboratory of Molecular Biology Home pagehttp://www2.mrc-lmb.cam.ac.uk/group-l... Research ThemeInterestsInformation transfer in the brain occurs at synapses where chemical transmitters are released from presynaptic terminals and are received by postsynaptic receptors. Glutamate is a major neurotransmitter and glutamate receptors are key to synaptic transmission and plasticity. Our research focuses on these receptors, in particular on the AMPA-type (AMPAR). AMPARs are the first to respond to glutamate and initiate synaptic signaling by depolarizing the postsynaptic membrane. AMPARs are unique as their rapid kinetics permit faithful decoding of high-frequency nerve impulses. Moreover, AMPAR are mobile and their trafficking is a major determinant of synaptic plasticity. Our ultimate aim is to understand how regulation of these receptors underlies learning and information storage at synapses. Towards this goal we are utilizing a variety of experimental approaches at different levels of complexity, ranging from the atomic structure of the receptor to its operation in neural networks. Research Focus
Equipmentcryo electron microscopy (cryo-EM) Electrophysiological recording techniques Field potential recording Fluorescence microscopy Molecular biology Protein purification superresolution microscopy Whole cell patch clamp X-ray crystallography Collaborators
Associated News Items
Key publicationsHerguedas B, Garcia-Nafria J, Cais O, Fernandez-Leiro R, Krieger J, Ho Ho, Greger IH. (2016), “Structure and organization of heteromeric AMPA-type glutamate receptors” Science doi: 10.1126/Science.aad3873 Publications2019Buonarati OR, Hammes EA, Watson JF, Greger IH, Hell JW. (2019), “Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation.” Sci Signal. eaar6889 Herguedas B, Watson JF, Ho H, Cais O, García-Nafría J, Greger IH. (2019), “Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP ?8.” Science eaav9011 Lee JY, Krieger J, Herguedas B, García-Nafría J, Dutta A, Shaikh SA, Greger IH, Bahar I. (2019), “Druggability Simulations and X-Ray Crystallography Reveal a Ligand-Binding Site in the GluA3 AMPA Receptor N-Terminal Domain.” Structure 27 2017Davies B et al (2017), “A point mutation in the ion conduction pore of AMPA receptor GRIA3 causes dramatically perturbed sleep patterns as well as intellectual disability.” Hum Mol Genet 26 Greger IH, Watson JF, Cull-Candy S (2017), “Structural and functional architecture of AMPA-type glutamate receptors and their auxiliary proteins” Neuron 94:713-730 Watson JF, Ho H, Greger IH (2017), “Synaptic transmission and plasticity require AMPA receptor anchoring via its N-terminal domain” eLife 2015Dutta A, Krieger J, Lee JY, Garcia-Nafria J, Greger IH, Bahar I (2015), “Cooperative Dynamics of Intact AMPA and NMDA Glutamate Receptors: Similarities and Subfamily-Specific Differences” Structure in pressGarcia-Nafria J, Hergueda B, Watson J, Greger IH (in press), “Structural dynamics of synaptic AMPA receptors” J. Physiol. 2015Krieger J, Bahar I, Greger IH (2015), “Structure, Dynamics, and Allosteric Potential of Ionotropic Glutamate Receptor N-Terminal Domains” Biophys. J 2014Cais O, Herguedas B, Krol K, Cull-Candy SG, Farrant M, Greger IH (2014), “Mapping the interaction sites between AMPA receptors and TARPs reveals a role for the receptor N-terminal domain in channel gating” Cell Reports 9, 728-40. PDF Shanks NF, Cais O, Maruo T, Savas JN, Zaika EI, Azumaya CM, Yates JR 3rd, Greger I, Nakagawa T (2014), “Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3.” J Neurosci 34(36):12104-20 Details 2013Balik A, Penn AC, Nemoda Z, Greger IH (2013), “Activity-regulated RNA editing in select neuronal subfields in hippocampus.” Nucleic Acids Res 41(2):1124-34 Details Herguedas B, Krieger J, Greger IH (2013), “Receptor heteromeric assembly-how it works and why it matters: the case of ionotropic glutamate receptors.” Prog Mol Biol Transl Sci 117:361-86 PDF Details Penn AC, Balik A, Greger IH (2013), “Reciprocal regulation of A-to-I RNA editing and the vertebrate nervous system.” Front Neurosci 7:61 Details Penn AC, Balik A, Greger IH (2013), “Steric antisense inhibition of AMPA receptor Q/R editing reveals tight coupling to intronic editing sites and splicing.” Nucleic Acids Res 41(2):1113-23 Details 2012Dutta A, Shrivastava IH, Sukumaran M, Greger IH, Bahar I (2012), “Comparative dynamics of NMDA- and AMPA-glutamate receptor N-terminal domains.” Structure 20(11):1838-49 Details Penn AC, Balik A, Wozny C, Cais O, Greger IH (2012), “Activity-mediated AMPA receptor remodeling, driven by alternative splicing in the ligand-binding domain.” Neuron 76(3):503-10 Details Shanks NF, Savas JN, Maruo T, Cais O, Hirao A, Oe S, Ghosh A, Noda Y, Greger IH, Yates JR 3rd, Nakagawa T (2012), “Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L.” Cell Rep 1(6):590-8 Details Sukumaran M, Penn AC, Greger IH (2012), “AMPA receptor assembly: atomic determinants and built-in modulators.” Adv Exp Med Biol 970:241-64 PDF Details 2011Jensen MH, Sukumaran M, Johnson CM, Greger IH, Neuweiler H (2011), “Intrinsic motions in the N-terminal domain of an ionotropic glutamate receptor detected by fluorescence correlation spectroscopy.” J Mol Biol 414(1):96-105 Details Rossmann M, Sukumaran M, Penn AC, Veprintsev DB, Babu MM, Greger IH (2011), “Subunit-selective N-terminal domain associations organize the formation of AMPA receptor heteromers.” EMBO J 30(5):959-71 Details Sukumaran M, Rossmann M, Shrivastava I, Dutta A, Bahar I, Greger IH (2011), “Dynamics and allosteric potential of the AMPA receptor N-terminal domain.” EMBO J 30(5):972-82 Details 2009Penn AC, Greger IH (2009), “Sculpting AMPA receptor formation and function by alternative RNA processing.” RNA Biol 6(5):517-21 PDF Details 2008Penn AC, Williams SR, Greger IH (2008), “Gating motions underlie AMPA receptor secretion from the endoplasmic reticulum.” EMBO J 27(22):3056-68 Details 2007Greger IH, Esteban JA (2007), “AMPA receptor biogenesis and trafficking.” Curr Opin Neurobiol 17(3):289-97 Details Greger IH, Ziff EB, Penn AC (2007), “Molecular determinants of AMPA receptor subunit assembly.” Trends Neurosci 30(8):407-16 PDF Details 2006Greger IH, Akamine P, Khatri L, Ziff EB (2006), “Developmentally regulated, combinatorial RNA processing modulates AMPA receptor biogenesis.” Neuron 51(1):85-97 Details 2003Greger IH, Khatri L, Kong X, Ziff EB (2003), “AMPA receptor tetramerization is mediated by Q/R editing” Neuron 40:763-774 Greger IH, Khatri L, Kong X, Ziff EB (2003), “AMPA receptor tetramerization is mediated by Q/R editing.” Neuron 40(4):763-74 Details 2002Greger IH, Khatri L, Ziff EB (2002), “RNA editing at Arg607 controls AMPA receptor exit from the endoplasmic reticulum” Neuron 34:759-772 |