Gunnersen laboratory: Neuron development and plasticity

Research Overview

Our broad research goal is to understand how neurons become connected to each other to form functional circuits. We investigate the formation of dendritic branches and synapses, the connections between neurons, in order to understand these processes in development and disease. Changes in the number and strength of synaptic connections (plasticity) are vital for the development of effective neuronal circuitry and for learning and memory in the healthy brain. On the other hand, abnormal synapse numbers and activity are defining features of neurological disorders. Learning more about dendrite and synapse development and function in the healthy brain will help us decipher the aberrant molecular pathways responsible for cognitive disorders such as mental retardation, epilepsy, schizophrenia and dementia.

Research in the Gunnersen laboratory is focussed on:

  1. the molecular and cellular mechanisms controlling synapse development,
  2. synapse loss in the earliest stages of Alzheimer’s disease and how this might be slowed or prevented,
  3. synapse formation/strengthening and how these processes contribute to the pathology of psychostimulant abuse and neuropathic pain.

Current investigations are focussed on members of the Seizure-related gene 6 (Sez6) family of proteins as we have uncovered important roles for Sez6 proteins in synapse development and maintenance. Altered Sez6 family gene function is associated with a number of neurological conditions including autism spectrum disorders (ASD), bipolar disorder, schizophrenia and febrile seizure. We are using a range of experimental approaches including inducible tissue-specific gene knockouts in mice, molecular biological and protein biochemical techniques to elucidate signalling mechanisms as well as behavioural and, together with collaborators, electrophysiological analyses.

If you have achieved excellent academic results and are interested in joining the lab as a PhD student, Honours student or Post-Doctoral researcher, please email Jenny Gunnersen.

Staff

Dr Jenny Gunnersen, Group Head
Dr Kathryn Munro, NHMRC/ARCDementia Research Development Fellow 2016-2019
Ms Kathleen Teng, Research Assistant, former Honours student 2012
Mr Chris Butler, PhD Student
Ms Yvette Wilson, PhD Student
Ms Amelia Nash, PhD Student, former Honours student 2014

Lab Alumni/Former Lab Members

Dr Maja Lovric, University of Melbourne McKenzie Post-Doctoral Fellow 2012-2015
Mr Eddy Yang, Undergraduate Research Student 2015
Ms Floriane Louboutin, Exchange MSc Student 2015
Ms Anja Sulaver, Exchange MSc Student 2015
Mr Ash Perera, Honours Student 2014
Ms Eve Perry, Undergraduate Research Student 2014
Ms Hasitha Pelenda, Undergraduate Research Student 2013
Ms Manon Audigé, Undergraduate Research Student 2013
Ms Teele Palumaa, Exchange Student, Research Technician 2012-2013
Ms Nissa Carrodus, Research Assistant 2010-2012 Ms Ashley Reynolds, Honours Student 2011

Collaborators

International

Prof Dr Stefan Lichtenthaler, TU Munich and DZNE, Germany
Prof Claudia Sommer, University of Würzburg, Germany
Prof Bart de Strooper, KU Leuven, Belgium
Dr Matthew Kennedy, Director Neuroscience Merck Research Labs, Boston, MA, USA
Dr Çagla Eroglu, Cell Biology, Duke University, NC, USA
Prof Michael Ehlers, Head of Global Neuroscience, Pfizer, Boston, MS, USA
Dr Matt Kennedy, Howard Hughes Medical Institute, Neurobiology, Duke University, NC, USA
Prof Peter Sonderegger, Dept of Biochemistry, Uni. of Zürich, Switzerland.

National

Dr Tim Aumann, Florey Institute of Neuroscience and Mental Health
Dr Stuart McDougall, Florey Institute of Neuroscience and Mental Health
Dr John Power, University of New South Wales
Dr Brett Graham, University of Newcastle
A-Prof Julian Heng, Harry Perkins Institute of Medical Research
Prof Seong-Seng Tan, Florey Institute of Neuroscience and Mental Health
Dr Jason Howitt, Florey Institute of Neuroscience and Mental Health
Dr Brett Collins, Institute of Molecular Bioscience, University of Queensland
Dr Andrea Bugarcic, Institute of Molecular Bioscience, University of Queensland

Funding

National Health and Medical Research Council (NHMRC)

2016-2018 NHMRC Project Grant 1099930: A potential analgesic target in a novel clinically-relevant neuropathic pain pathway. CIA Dr Jenny Gunnersen, CIB Dr Stuart McDougall, CIC Prof Annette Dolphin. $685,811.
2014-2016 NHMRC Project Grant1058672: Investigating secondary effects of a promising therapeutic strategy for Alzheimer's disease. CIA Dr Jenny Gunnersen, CIB Prof Stefan Lichtenthaler, CIC Dr Tim Aumann. $677,527.
2011-2013 NHMRC Project Grant 1008046: Sez6 and neuronal calcium signalling in synapse development. CIA Dr Jenny Gunnersen, CIB Dr John Power. $596,072.
2011-2013 NHMRC Project Grant 1008787: The role of ubiquitin ligase adaptor protein Ndfip1 in neuronal development. CIA Dr Jenny Gunnersen, CIB  Dr Jason Howitt. $561,732.
2009-2011 NHMRC Project Grant 566620: Mechanisms controlling interneuron migration and layering in the cortex. CIA Dr Vicki Hammond, CIB Dr Jenny Gunnersen. $588,750.
2007-2009 NHMRC Project Grant 454462: Sez6 signalling mechanisms and function in the developing neocortex. CIA Dr Jenny Gunnersen, CIB Dr Vicki Hammond, CIC Dr Joanne Britto $480,250.
2005-2007 NHMRC New Investigator Project Grant 350296: Neuronal assembly in the developing brain. CIA Dr Jenny Gunnersen, CIB Dr Vicki Hammond. $640,500.

Research Opportunities

This research project is available to PhD students to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Publications

  • Butler CW, Wilson YM, GUNNERSEN JM, Murphy M.  Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning. Learn Mem 2015; 22(8): 370-84.
  • Simon CM*, Rauskolb S*, GUNNERSEN JM*, Holtmann B, Drepper C, Dombert B, Braga M, Wiese S, Jablonka S, Pühringer D, Zielasek J, Hoeflich A, Silani V, Wolf E, Kneitz S, Sommer C, Toyka KV, Sendtner M.  Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy. Acta Neuropathol 2015; 130(3): 373-87. *Equal 1st authors.
  • Howitt J, Low LH, Putz U, Doan A, Lackovic J, Goh CP, GUNNERSEN J, Silke J, Tan SS.  Ndfip1 represses cell proliferation by controlling Pten localization and signaling specificity. J Mol Cell Biol 2015; 7(2): 119-31.
  • Hammond VE*, GUNNERSEN JM*, Goh CP, Low LH, Hyakumura T, Tang MM, Britto JM, Putz U, Howitt JA, Tan SS.  Ndfip1 Is Required for the Development of Pyramidal Neuron Dendrites and Spines in the Neocortex. Cereb Cortex 2014; 24(12): 3289-300. *Equal 1st authors.
  • Ngo  L, Haas M, Qu Z, Li SS, Zenker J, Teng KS-L, GUNNERSEN JM, Breuss  M, Habgood M, Keays D, Heng J I-T. TUBB5 and its disease-associated mutations influence the terminal differentiation and dendritic spine densities of cerebral cortical neurons. Hum Mol Genet 2014; 23(19): 5147-58.
  • Carrodus NL, Teng K S-L, Munro KM, Kennedy MJ, GUNNERSEN JM.  Differential labeling of cell-surface and internalized proteins after antibody feeding of live cultured neurons. J Vis Exp 2014 Feb 12;(84). doi: 10.3791/51139.
  • GUNNERSEN JM, Kuek A, Phipps JA, Hammond VE, Puthussery T, Fletcher EL, Tan SS.  Seizure-related gene 6 (Sez-6) in amacrine cells of the rodent retina and the consequence of gene deletion. PLoS ONE 2009; 4(8): e6546
  • GUNNERSEN JM, Kim MH, Fuller SJ, De Silva M, Britto JM, Hammond VE, Davies, PJ, Petrou S, Faber ESL, Sah P, Tan SS.  Sez-6 proteins affect dendritic arborization patterns and excitability of cortical pyramidal neurons. Neuron 2007; 56: 621-639.
  • Vallotton P, Lagerstrom R, Sun C, Buckley M, Wang D, De Silva M, Tan SS, GUNNERSEN J.  Automated analysis of neurite branching in cultured cortical neurons using HCA-Vision. Cytometry 2007; (Part A) 71: 889-895.
  • GUNNERSEN JM, Augustine C, Spirkoska V, Kim M, Brown M, Tan SS. Global analysis of gene expression patterns in developing mouse neocortex using Serial Analysis of Gene Expression (SAGE). Mol Cell Neurosci 2002; 19: 560-573.
  • GUNNERSEN JM, Spirkoska V, Smith PE, Danks RA, Tan SS.  Growth and migration markers of rat C6 glioma cells identified by Serial Analysis of Gene Expression. Glia 2000; 32: 146-154.
  • Wiese S*, Digby MR*, GUNNERSEN JM, Gotz R, Pei G, Holtmann B, Lowenthal J, Sendtner M.  The anti-apoptotic protein ITA is essential for NGF-mediated survival of embryonic chick neurons. Nature Neurosci 1999; 2: 978-983.