Synaptic MicroRNAs

Schratt Lab

phone: +49 (0)6421-28-65020 email: gerhard.schratt@staff.uni-marburg.de

In our lab, we are using an integrative approach, combining biochemical, cell biological and mouse genetic approaches, to study the function and regulation of microRNAs in postsynaptic development and plasticity.
Research
Project 1: microRNA transport and processing Project-AIn this project, we want to understand the molecular mechanisms underlying the specific subcellular localization of (pre-)microRNAs in neurons. Using microarray and deep sequencing, we identified subsets of (pre-)microRNAs that are enriched in the nucleus (a) or synapto-dendritic compartment (b). We are currently investigating the mechanisms of directed transport and local processing of (pre-)miRNAs and their relevance for the local control of gene expression in neuronal compartments. Techniques: (small) RNAseq, single molecule in situ hybridization, live imaging     Project 2: microRNA-associated RISC (miRISC) activity Project-B_RISC-regulationIn this project, we are exploring different mechanisms whereby neuronal activity can regulate miRNA activity at the level of miRISC. The current focus is on the modulatory role of RNA-binding proteins (a), miRISC localization to intracellular membranes (b) and the role of competing endogenous RNAs (c). Techniques: siRNA screening, CLIPseq, confocal imaging         Project 3: miRNA function in neuronal homeostasis Project-CIn this project, we want to understand how miRNA-dependent regulation of neuronal targets contributes to homeostatic forms of synaptic plasticity. We have identified a large miRNA cluster that is required for homeostatic synaptic depression, and are currently trying to characterize the relevant targets and the physiological significance. Techniques: quantitative proteomics, ribosome profiling, electrophysiology           Project 4: miRNAs in brain physiology/pathology Project-D_Mouse-experimentsIn this project, we are using genetically modified mouse models to explore the function of specific miRNAs during brain development and in adult behavior. In addition, we are studying a mouse model for schizophrenia with impaired miRNA biogenesis. We are particularly interested in potential cognitive and social impairments in these mice with links to neurodevelopmental (e.g. autism) and neuropsychiatric (e.g. schizophrenia, depression) disorders. Techniques: histology, behaviour, electrophysiology
Team

Postdocs


Cecilia-Carmen Patrascan

Silvia Bicker

Anna Antoniou

Marek Rajman

Sharof Khudayberdiev

Roberto Fiore

PhD Students


Martin Lackinger

Reeta Daswani

Helena Martins

Federico Zampa

Kerstin Weiss

Lab technicians


Eva Becker

Gertraud Jarosch

Maria-Bettina Kowalksi

Renate Gondrum

Heinrich Kaiser

Ute Beck

Selected Publications
  • Rajman M, Metge F, Fiore R, Khudayberdiev S, Aksoy-Aksel A, Bicker S, Ruedell Reschke C, Raoof R, Brennan GP, Delanty N, Farrell MA, O’Brien DF, Bauer S, Norwood B, Veno MT, Krüger M, Braun T, Kjems J, Rosenow F, Henshall DC, Dieterich C, Schratt G. A microRNA-129-5p/Rbfox crosstalk coordinates homeostatic downscaling of excitatory synapses. EMBO J. 2017 May 9. pii: e201695748. doi: 10.15252/embj.201695748 – pdf
  • Brenes JC, Lackinger M, Höglinger GU, Schratt G, Schwarting RK, Wöhr M. (2015) Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats. J Comp Neurol., DOI: 10.1002/cne.23842.
  • Störchel PH, Thümmler J, Siegel G, Zampa F, Sumer S, Schratt G. (2015) A large scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function. EMBO J 34(17):2237-54.
  • Olde Loohuis NF, Ba W, Stoerchel PH, Kos A, Jager A, Schratt G, Martens GJ, van Bokhoven H,Nadif Kasri N, Aschrafi A. (2015) MicroRNA-137 Controls AMPA-Receptor-Mediated Transmission and mGluR-Dependent LTD. Cell Rep. 11(12):1876-84.
  • Valluy J, Bicker S, Aksoy-Aksel A, Lackinger M, Sumer S, Fiore R, Wüst T, Seffer D, Metge F, Dieterich C, Wöhr M, Schwarting R, Schratt G. (2015) A coding-independent function of an alternative Ube3a transcript during neuronal development, Nature Neuroscience 18(5):666-73.
  • Peykov S, Berkel S, Schön M, Weiss K, Weiss B, Schratt G, Noethen M, Boeckers TM, Rietschel M, Rappold GA. Identification and functional characterization of rare SHANK2 variants in schizophrenia, Mol. Psychiatry, 2015 Jan 6. doi: 10.1038/mp.2014.172. [Epub ahead of print].
  • Fiore R, Rajman M, Schwale C, Bicker S, Antoniou A, Bruehl C, Draguhn A, Schratt G. (2014) miR-134-dependent regulation of Pumilio2 is necessary for homeostatic synaptic depression, EMBO J, 33(19):2231-46. Khudayberdiev S, Zampa F, Rajman M and Schratt G (2013)
  • A comprehensive characterization of the nuclear microRNA repertoire of post-mitotic neurons.
    Front. Mol. Neurosci. 6: 43.
  • Bicker S, Khudayberdiev S, Weiss K, Zocher K, Baumeister S, Schratt G. (2013)
    The DEAD-box helicase DHX36 mediates dendritic transport of the neuronal precursor-microRNA-134.
    Genes Dev 27:991-996
  • Saba, R., Störchel, P.H., Aksoy-Aksel, A., Kepura, F., Lippi, G., Plant, T.D. and Schratt, G. (2012)
    The dopamine-regulated microRNA, miR-181a, controls GluA2 surface expression in hippocampal neurons.
    Mol Cell Biol. 32(3):619-32.
  • Siegel, G., Saba R. and Schratt G., (2011)
    microRNAs in neurons: manifold regulatory roles at the synapse.
    Curr Opin Genet Dev. 21(4):491-7.
  • Christensen, M., Larsen, L.A., Kauppinen, S. & Schratt G. (2010)
    Recombinant adeno-associated virus-mediated microRNA delivery into the postnatal mouse brain reveals a role for miR-134 in dendritogenesis in vivo.
    Frontiers in Neural Circuits,3:16.
  • Schratt, G. (2009)
    microRNAs at the synapse.
    Nat Rev Neurosci. 10(12): 842-9.
  • Schratt G. (2009)
    Fine-tuning neural gene expression with microRNAs.
    Curr. Op. Neurobiol., 19(2):213-9.
  • Siegel G.*, Obernosterer G.*, Fiore R., Oehmen, M., Bicker, S., Christensen M., Khudayberdiev, S., Leuschner, P., Busch, C., Kane, C., Hübel K., Dekker, F., Hedberg, C., Rengarajan, B., Drepper, C., Waldmann H., Kauppinen S., Greenberg M.E., Draguhn, A., Rehmsmeier M., Martinez J. and Schratt G.  (2009)
    A functional microRNA screen implicates miR-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis.
    Nature Cell Biology (Article), 11(6):705-716.
  • Fiore R.*, Khudayberdiev S.*, Christensen M., Siegel G., Flavell S., Kim T.K., Greenberg M.E. and Schratt G. (2009)
    Mef2-dependent activation of the miR-379-410 cluster promotes dendritic outgrowth by fine-tuning protein levels of the translational repressor Pumilio2. EMBO J.18;28(6):697-710.
  • Schratt G, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M and Greenberg ME. (2006)
    A brain-specific microRNA regulates dendritic spine development.
    Nature (Article), 439(7074):283-9.


Cecilia has a Biochemistry Engineering degree at the Babes-Boylai University, Cluj-Napoca, Romania and Master of Science in Molecular Bioengineering, specialising in Tissue Engineering at the Technical University of Dresden, Germany. The experimental part of the Master’s Thesis was done in the Biomaterial Department of the Max Bergmann Center of Biomaterials, Dresden, where she developed a novel biocompatible polymer able to replace human injured skin.
She completed her PhD studies in Medicine – Allergic Immunology at the Philipps University of Marburg, Biomedical Research Center, Germany. She focused on epidemiological data concerning the differences in the development of immune systems of children growing-up in farming and non-farming environments.
Moreover, as a qualified Teacher she taught General Chemistry and Basics Biochemistry at the IX. and X. Class Highschool in Cluj-Napoca, Romania. Currently, she is Supervisor in Biochemistry Seminars and Practice for dentist-and medical students from Medicine Faculty. Likewise, she shows interest for Neuroscience with focus on microRNA research and its role in psychiatric disorders such as Schizophrenia.
email: cecilia-carmen.patrascan@staff.uni-marburg.de
Silvia studied Molecular Biology at the University of Vienna, Austria, and did her Diploma thesis in the lab of Prof. Sieghart at the Center for Brain Research, Medical University of Vienna. Her PhD project in the Schratt lab aimed at elucidating how dendritic miRNAs reach their final destination to regulate local protein synthesis at the synapse. This work led to the discovery of a novel form of miRNA transport to dendrites, occurring at the level of the miR-134 precursor (pre-miR-134) and involving the DEAH-box helicase DHX36. Currently, Silvia focuses on identifying the molecular mechanisms underlying activity-dependent transport and subsequent local processing of the pre-miR-134/DHX36 complex.
email: silvia.bicker@staff.uni-marburg.de
During her PhD Anna explored novel aspects of PICK1 in neurons, a protein that mediates AMPA receptor-trafficking and regulates the actin cytoskeleton in dendritic spines. Due to a long-standing interest in RNA-dependent regulatory mechanisms, she is exploring the sub-cellular localisation of the RNA-induced silencing complex in neuronal dendrites and local regulation of microRNA-guided post-transcriptional gene silencing in synaptic plasticity.
Marek joined Gerhard Schratt’s group in September 2011. He is studying the regulation of new protein synthesis during homeostatic plasticity in neurons using quantitative proteomics. In general he is interested how features of 3′UTRs, miRNAs and RNA binding proteins regulate protein translation or mRNA transport in neurons.
email: marek.rajman@staff.uni-marburg.de
Sharof studied biology (Bachelor’s) and biotechnology (MSc) at the Samarkand State University (Uzbekistan). He also graduated international Master’s program in Molecular and Cellular biology at the Heidelberg University, where he got interested in the mechanism of transcriptional regulation of microRNA expression in neurons. Currently, he is performing the PhD work related to the activity-dependent regulation of microRNAs in different subcellular compartments of neurons.
email: sharof.khudayberdiev@staff.uni-marburg.de
I am interested in understanding the cellular mechanisms of activity-dependent regulation of neuronal microRNAs and to determine how this regulation affects neuronal development and plasticity. So far primary hippocampal neurons have been my main model system. Now I now plan to complement the in vitro experiments with in vivo approaches, since genetic models and the tools to ectopically manipulate microRNA activity in the intact brain have become available.
email: roberto.fiore@staff.uni-marburg.de
Martin studied “Cell Biology” (B.Sc.) at the University of Osnabrück specialized on microbiology (immunology) and neurobiology. In 2010 he made his Bachelor Thesis in the Brandt Group http://www.biologie.uni-osnabrueck.de/arbeitsgruppen/neurobiologie.html focusing on microtubule assembly mechanisms (neurodegeneration; tauopathies).
After his B.Sc. he studied “Biomedical Science” (main focus on Neurobiology, M.Sc.) at the Philipps University Marburg. He joined the Schratt lab for his Master Thesis to investigate the regulation of neuronal microRNA and spine growth in an AAV-construct in-vitro. Since 2012 he is PhD student in this lab to phenotype miRNA knockout mice models on molecular levels and established behavioral technique to screen animals in the light of neurology and neuropsychiatric diseases. Besides that, Martin is vice-speaker of the Junior GBM Marburg (Gesellschaft für Molekularbiologie und Biochemie e.V.) http://www.gbm-online.de/.
email: lackingm@staff.uni-marburg.de
After graduating in Biotechnologies (B.Sc.), Reeta persued her interest in studying brain functions at a behavioral and molecular level. She graduated in 2014 in Neurobiology (M.Sc.) at “La Sapienza” University of Rome focusing her attention on the implication of microRNAs in the behavioral variability found in post-traumatic stress disorder.
She joined in 2015 the lab of Prof. Schratt in Marburg as a PhD student to investigate the role of a specific microRNA in the long term memory formation and consolidation.email: reetu.daswani@staff.uni-marburg.de
Helena studied Biochemistry (B.Sc) and Cellular and Molecular Biology (M.Sc) with a great focus on neurobiology at the University of Coimbra, Portugal. To fulfill her deep interest in microRNAs she joined Prof. Schratt lab where she is a PhD student since March 2015. It is her goal to study how microRNAs are regulated in neuropsychiatric disorders.
Federico completed his studies in 2010 within the international master´s degree program in Neuroscience at the University of Trieste and worked for one and a half years as post-graduate student. Since October 2012 he is PhD student in the lab of Prof. Schratt in Marburg, where he studies the dynamics of microRNAs biogenesis and localization in neurons.
Kerstin studied biology (B.Sc.) and molecular biosciences (with the focus neuroscience, M.Sc.) at the University of Heidelberg. She joined the Schratt group for her master thesis in 2010 and started as a PhD student in Marburg in 2011.
She is working with animal and cellular models to understand the expression and function of miRNAs in the brain and their role in synaptic mechanisms.
email: kerstin.weiss@staff.uni-marburg.de