Systems Biology

mara-dierssen
Cellular and Systems Neurobiology

Group Structure

GROUP LEADER:
Mara Dierssen
POSTDOCTORAL FELLOWS:
María Martínez de Lagrán, Thomas Gener, Susanna Molas, Belén de Sancristóbal
TECHNICIAN:
Tiziana Pederzani
PhD STUDENTS:
Davide D’Amico (until November 2013), Meritxell Pons (until October 2013), Silvina Catuara, Marta Fructuoso, Linus Manubens

Summary

The Dierssen’s lab is interested on understanding cognition and behaviour as emergent properties of the neuronal networks and how genetic perturbation in mental disorders modify the way the brain integrates information to produce behaviour. Alterations in the architectural properties of the neurons are observed in most mental disorders and are assumed to be the cause of the cognitive disturbances. Thus, the main question in the field remains how the dendritic tree architecture constrains the network activity and influences cognition. We focus mainly on intellectual disability and neuropsychiatric disorders, using a systems neuroscience approach that combines behavioural and neurobiological analyses in mice, with the results from cellular models. This systematic and wide-angled approach with different levels of description, has led us to build an integrated view of how the phenomic profiles correlate with cellular and molecular alterations in the neurons of these mouse models. This is a realistic stepping-stone towards unravelling the biological codes behind mental disorders. The value of our studies lies also in its translational angle. Based on our understanding of the genetic and molecular circuits disturbed in intellectual disability we have initiated a clinical trial in Down syndrome (de la Torre et al., 2013) and fragile X syndrome (FRAXA Foundation). Examining individual brain regions, neural circuits and molecules has brought us a long way, but it alone cannot explain the workings and malfunction of the brain. Thus, our future plans are to integrate behavioural, physiological and cellular quantitative measurements with computer modelling. We are confident that this new line will allow us to generate an innovative and powerful analytical platform that will lead us to significant breakthroughs in the neurobiology of mental disorders.
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Research Projects

  • Brain operation in intellectual disability
    • (i) Neuronal network architecture and learning plasticity
      María Martínez de Lagrán, Silvina Catuara
    • (ii) Computational modelling of dynamical brain states in intellectual disability
      Belén de Sancristóbal, Linus Manubens
    • (iii) Molecular constrains/biomarkers
      Laura Xicota, Mireia Ortega
  • Neuronal codes behind neuropsychiatric disorders
    • (i) Panic disorder: why the brain works in “anxious mode”
      Thomas Gener
    • (ii) Nicotine dependence: what combinatorial expression changes of ion channel genes increase tobacco consumption?
      Susanna Molas
    • (iii) Obsessive-compulsive behavioural components of obesity: phenotypic roadmap of obesity pandemics
      Marta Fructuoso
  • Computational tools for longitudinal phenotype recordings
    Jose Antonio Espinosa, Marcos Quevedo

Selected Publications

  1. Mellström B, Sahún I, Ruiz-Nuño A, Murtra P, Gomez-Villafuertes R, Savignac M, Oliveros JC, Gonzalez P, Kastanauskaite A, Knafo S, Zhuo M, Higuera-Matas A, Errington ML, Maldonado R, Defelipe J, Jefferys JG, Bliss TV, Dierssen M, Naranjo JR.
    “DREAM controls the on/off switch of specific activity-dependent transcription pathways.”
    Mol Cell Biol, doi: 10.1128/MCB.00360-13. Epub 2013 Dec 23.
  2. Mouton-Liger F, Sahún I, Collin T, Lopes Pereira P, Masini D, Thomas S, Paly E, Luilier S, Même S, Jouhault Q, Bennaï S, Beloeil JC, Bizot JC, Hérault Y, Dierssen M, Créau N.
    “Developmental molecular and functional cerebellar alterations induced by PCP4/PEP19 overexpression: Implications for Down syndrome.”
    Neurobiol Dis, doi: 10.1016/j.nbd.2013.11.016. Epub 2013 Nov 28.
  3. Del Pino I, García-Frigola C, Dehorter N, Brotons-Mas JR, Alvarez-Salvado E, Martínez de Lagrán M, Ciceri G, Gabaldón MV, Moratal D, Dierssen M, Canals S, Marín O, Rico B.
    “Erbb4 Deletion from Fast-Spiking Interneurons Causes Schizophrenia-like Phenotypes.”
    Neuron, 79(6):1152-68 (2013).
  4. Santos M, D’Amico D, Spadoni O, Amador-Arjona A, Stork O, Dierssen M.
    “Hippocampal Hyperexcitability Underlies Enhanced Fear Memories in TgNTRK3, a Panic Disorder Mouse Model.”
    J Neurosci, 33(38):15259-71 (2013).
  5. De la Torre R, De Sola S, Pons M, Duchon A, de Lagran MM, Farré M, Fitó M, Benejam B, Langohr K, Rodriguez J, Pujadas M, Bizot JC, Cuenca A, Janel N, Catuara S, Covas MI, Blehaut H, Herault Y, Delabar JM, Dierssen M.
    “Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans.”
    Mol Nutr Food Res, doi: 10.1002/mnfr.201300325. Epub 2013 Sep 14.