22.11.2017 13:00

Neurobiology / FOR2289 Lecture:

 

Fibroblast growth factor signalling: cause or consequence of axonal loss in multiple sclerosis?

Prof. Christopher Linington
Institute of Infection, Immunity and Inflammation
University of Glasgow, UK

 

Different place:

SR25
Im Neuenheimer Feld 328
Heidelberg

 

Dysregulation of fibroblast growth factor signalling is implicated in a growing number of neurological and psychiatric disorders associated with loss of white matter integrity[1-4]. These include multiple sclerosis (MS) in which astrocytes up regulate expression of fibroblast growth factor 9 (FGF9) at sites of ongoing tissue damage[4]. To explore how this contributes to lesion development we injected adeno-associated virus constructs encoding FGF9 (AAV-FGF9) or EGFP (EGFP-AAV) under the control of a GFAP promotor into the motor cortex of naïve adult rats. AAV-FGF9, but not AAV-EGFP injected animals developed demyelinated lesions that recapitulated many features associated with smouldering lesions in patients with progressive multiple sclerosis. Specifically these lesions develop over several months and are associated with pronounced neuronal/axonal loss, low grade microglial activation, astrocyte hypertrophy, and critically, develop in the absence of large numbers of recruited lymphocytes recruited from the periphery. Neuronal loss is an early feature of lesion development in this model, but the precise relationship between demyelination and axonal/neuronal loss remained unclear. We therefore investigated the pathogenic potential of FGF9 in myelinated cultures derived from embryonic spinal cord. In this in vitro system FGF9 failed to induce primary demyelination but after ten days we observed numerous swellings reminiscent of those associated with axonal transport defects in several neurodegenerative conditions. A comparative gene microarray study revealed this FGF9-mediated effect was associated with transcription fingerprint characterised by downregulation of numerous neuronal transcripts encoding products associated with maintenance of axonal structure and function. These included neurofilaments, tubulin (Tubb3), motor proteins (Kif5a, Dnahc6), as well as axonal cargos required to maintain axonal (Scn1a, Scn3b, Scnb2) and synaptic function (Bsn, Pclo, Sv2b, Syn). This transcriptional response was unique to FGF9, as it was not observed in cultures treated with FGF1 or FGF2. Our data suggest the primary pathogenic effect of FGF9 is to compromise neuronal health resulting in axonal deficits, loss of function and, if sustained for prolonged periods irreversible axonal/neuronal loss. Support for this hypothesis was obtained using cultured post-mitotic cortical neurons in which FGF9 down regulates expression of neurofilaments and axonal motor proteins; an effect associated with loss/retraction of dendrites and reduced neuronal survival. We suggest treatments already in development to target FGF signalling in other diseases should be investigated to determine if they will slow or even reverse loss of function in multiple sclerosis and psychiatric disorders associated with increased availability of FGF9 in the CNS.

References:
[1]Terwisscha van Scheltinga et al. (2013) Fibroblast growth factors in neurodevelopment and psychopathology. Neuroscientist. 19(5):479-94.
[2]Aurbach et al. (2015) Fibroblast growth factor 9 is a novel modulator of negative affect. Proc Natl Acad Sci U S A. 112(38):11953-8.
[3]Evans et al. (2004) Dysregulation of the fibroblast growth factor system in major depression. Proc Natl Acad Sci U S A. 101(43):15506-11.
[4]Lindner et al. (2015) Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9 Brain. 138(Pt 7):1875-93.

 

29.11.2017 13:00

Neurobiology / SFB1134 Lecture:

 

Songbirds' solution to an intractable motor learning problem

Richard Hahnloser
Institute of Neuroinformatics
University of Zurich and ETH Zurich, Switzerland

 

While acquiring motor skills, such as courtship songs and dances, animals must match their performance to a desired target. However, because both the structure and the temporal position of individual gestures are adjustable, the number of possible motor transformations increases exponentially with sequence length, and searching for the optimal transformation quickly becomes computationally intractable. We tested how zebra finches cope with the computational complexity of song learning, by prompting juveniles to modify their song to correct conflicting phonological and sequential mismatches in song syllables. Surprisingly, birds matched each syllable to the most acoustically similar sound in the target, regardless of its temporal position, resulting in sequence errors that were later corrected. Thus, birds prioritized efficient learning of syllable vocabulary, at the cost of inefficient syntax learning. This modular strategy amounts to a linear workaround of an intractable quadratic problem, and could perhaps be a generic solution in the evolution of motor learning mechanisms.
 

HS2
Im Neuenheimer Feld 306
Heidelberg

 

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Biotech-Ausgründung des Instituts für Neurobiologie in Start-up-Wettbewerb erfolgreich

Die FundaMental Pharma GmbH gehört zu den Gewinnern des „BioRiver Boost!“-Wettbewerbs 2017

Prof. Dr. Hilmar Bading (rechts) und der Biologe Dr. Thomas Schulze.
Foto: Frank Wiedemeier / BioRiver

Die FundaMental Pharma GmbH, eine Biotech-Ausgründung des Instituts für Neurobiologie der Universität Heidelberg, gehört zu den Gewinnern des „BioRiver Boost!“-Wettbewerbs 2017. Der Branchenverband „BioRiver – Life Science im Rheinland“ kürt damit die besten Start-ups im Bereich der Lebenswissenschaften und der Biotechnologie. Das junge Unternehmen aus Heidelberg überzeugte die Jury mit seiner Arbeit an einem kombinierten Wirkstoff-Applikationssystem, das zur Neuroprotektion eingesetzt werden soll. Ziel ist es, degenerative Prozesse im Gehirn aufzuhalten. Insgesamt drei Gründungsprojekte wurden unter den acht Finalisten aus Deutschland und Europa als Sieger ausgewählt.

Das Unternehmen FundaMental Pharma wurde im April 2016 von den beiden Neurobiologen Prof. Dr. Hilmar Bading und Juniorprofessorin Dr. Daniela Mauceri sowie dem Biologen Dr. Thomas Schulze gegründet. „Wir verstehen den Preis als Bestätigung unserer grundlegenden wissenschaftlichen Idee, ein neues Therapieprinzip zur Behandlung bislang nicht therapiefähiger neurodegenerativer Erkrankungen zu etablieren“, erklärt Prof. Bading. Mehr…


Heidelberg scientists gain new insights into the development of the vascular system

The findings of this basic research could provide new ways of treating diseases that involve a dysfunctional formation of blood vessels.

ruizResearchers in the team of Dr Carmen Ruiz de Almodóvar Externer Inhalt of the Heidelberg University Biochemistry Center have discovered a crucial biological step that regulates the formation of blood vessels. They were able to show that the proteins YAP and TAZ play an important role in this process.

Endothelial cells form the inner lining of blood vessels. During embryonic development, these cells begin to assemble and grow into vessels. Genetic dysfunction of YAP and TAZ specifically in endothelial cells results in severe vascular defects right up to the death of the embryo, as shown by the postdoctoral researcher Dr Xiaohong Wang, who works in the team of Dr Ruiz de Almodóvar.

YAP and TAZ are the effectors of the Hippo signalling pathway, which has been identified as a central regulator of organ size and tumour growth. As co-transcription factors, the two proteins bind to certain transcription factors to regulate gene transcription, the process by which genetic information is copied from DNA to RNA to ultimately result in specific protein formation. In order to do this, YAP and TAZ must be activated and move to the cell nucleus.

As the Heidelberg scientists discovered, the “Vascular Endothelial Growth Factor” (VEGF) – a key factor for the growth and development of blood vessels – is a major activator for YAP and TAZ in endothelial cells. The researchers examined the process of vascularisation of the central nervous system in mice. “If YAP and TAZ are missing, the endothelial cells will not react to the VEGF signal, preventing correct blood vessel formation,” explains Dr Ruiz de Almodóvar.

YAP/TAZ Orchestrate VEGF Signaling during Developmental Angiogenesis
Developmental Cell (published online 31 August 2017)


Preisverleihungen an IZN Nachwuchswissenschaftler

Anlässlich des jährlichen Retreats des Interdisziplinären Zentrums für Neurowissenschaften (IZN) im Kloster Schöntal wurde am 10.07.17 zum zweiten Mal der IZN Chica and Heinz Schaller Young Investigator Neuroscience Award für eine herausragende Publikation auf dem Gebiet der Neurowissenschaften vergeben. Der Preis ist mit 1.000 Euro dotiert und benannt nach den Stiftern, Frau Professor Chica Schaller und Herrn Professor Heinz Schaller (†2010), die beide am Wissenschaftsstandort Heidelberg tätig waren und als Pioniere der modernen Molekularbiologie und Neurobiologie gelten.

2017-chs-preis-scheck-small
Ricarda Diem, Priit Pruunsild
Foto: Romina Geiger

Preisträger ist Herr Dr. Priit Pruunsild, der am Institut für Neurobiologie des IZN Heidelberg seit 2012 forscht. Er wurde für seine 2017 in der Zeitschrift „Cell Reports“ erschienene Arbeit „Networks of Cultured iPSC-Derived Neurons Reveal the Human Synaptic Activity-Regulated Adaptive Gene Program“ ausgezeichnet. Das Preiskomitee begründet seine Entscheidung wie folgt:  Die Arbeit von Herrn Dr. Pruunsild zeigt einen potentiell bedeutsamen Weg in der evolutionären Entwicklung komplexer kognitiver Fähigkeiten des Menschen. Ein Vergleich mit dem Nervensystem der Maus ergab, dass das der Menschen ein erweitertes Repertoire an Genen besitzt, deren Expressionslevel über synaptische Aktivität reguliert wird. Das schafft, einfach ausgedrückt, zusätzliche Möglichkeiten Informationen zu speichern und zu verarbeiten. Um dies nachzuweisen, wurden State-of-the-Art molekularbiologische und elektrophysiologische Methoden eingesetzt und in einem ausgeklügelten Versuchsplan kombiniert.

Herr Dr. Pruunsild arbeitet seit 2012 als wissenschaftlicher Mitarbeiter am Institut für Neurobiologie Heidelberg in der Arbeitsgruppe von Professor Hilmar Bading. Zuvor war er an der University of Technology in Tallinn wissenschaftlich tätig, wo er auch seine PhD-Arbeit durchführte.

Der IZN Chica and Heinz Schaller Young Investigator Neuroscience Award wird weiterhin jährlich mit einer Bewerbungsfrist Ende Mai oder Juni ausgelobt werden. Informationen dazu finden sich einige Wochen zuvor auf der Homepage des IZN.

2017-brainaid-prize-small
H. Bading, C. Depp, C. Schuster
Foto: Romina Geiger

Frau Constanze Depp wurde mit dem Foundation BrainAid IZN Master’s Award ausgezeichnet. Mit diesem Preis, der dieses Jahr zum erstem Mal von der Stiftung BrainAid vergeben wurde, ehrt die Auswahlkommission unter Vorsitz von Professor Christoph Schuster die Arbeit von Constanze Depp über den Zusammenhang zwischen Kalziumsignalen und oxidativer Schädigung von Mitochondrien. In ihrer Masterarbeit am Institut für Neurobiologie, betreut von Dr. Carlos Bas Orth, konnte Frau Depp aufklären, wie synaptische Aktivität und die damit einhergehende Änderung der neuronalen Genexpression zu einem Schutz der Mitochondrien vor oxidativem Stress führen. Diese Erkenntnisse liefern einen wichtigen Beitrag zum Verständnis neurodegenerativer Prozesse im Gehirn.

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Open positions at the IZN

  • The research group of Kevin Allen Externer Inhalt is seeking a highly motivated master student to work on the neuronal basis of spatial behaviour. The group is based within the Department of Clinical Neurobiology, Medical Faculty Heidelberg and DKFZ. Adobe
    posted 10.2017
  • The group of Daniela Mauceri Externer Inhalt is offering a Master thesis studying the "Role of synaptic activity in the regulation of the lipid content and fluidity of neuronal plasma membrane". This is an interdisciplinary project, bridging the neurobiology and biochemistry fields. Adobe
    posted 08.2017
  • The group of Wolfgang Sommer Externer Inhalt at the ZI Mannheim is looking for 2 lab rotation students as part of the "SFB1134 – Functional Ensembles" project using either electrophysiology or behavior-study methods with the possibilty of continuation for Master theses.
    E-physAdobe  BehaviorAdobe
    posted 08.2017
  • The group of Carmen Ruiz de Almodóvar Externer Inhalt is offering a PhD and/or Postdoc project with the title "Neuro-vascular communication in the central nervous system" to further understand how different neuronal populations control CNS vascularization and how the vasculature integrates into the CNS and aims to identify the molecular mechanisms of this regulation.  Adobe  posted 08.2017
  • A postdoc/scientific assistant position is offered in General Neurophysiology (Prof. Dr. Oliver Kann Externer Inhalt) at the Institute of Physiology and Pathophysiology, University of Heidelberg.
    The group of Professor Kann focuses on (i) the neuronal energy metabolism and (ii) the impact of brain macrophages (microglial cells) on neuronal activity under physiological and pathophysiological conditions. The future position holder will carry out an own research project within one of the two research focuses of the group.  Adobe  posted 07.2017
  • The Department of Cellular and Molecular Pathology, DKFZ Heidelberg (Prof. Dr. H.-J. Gröne, sub-group Viola Nordström Externer Inhalt) is seeking two exceptionally motivated and skilled students (m/f) for Master theses in Neurobiology, offering the possibility to investigate the regulatory membrane lipid microenvironment of Astrocytes in the fascinating field of obesity, neuroinflammation and Alzheimer’s disease (AD).  Adobe  posted 05.2017
  • A master thesis position is available in the laboratory of Carmen Ruiz de Almodóvar Externer Inhalt studying the role of Angiopoietins in the developing cerebellum.  Adobe  posted 04.2017
  • A postdoctoral position in Neurobiology and Alzheimer Research is available in the laboratory of Prof. Ulrike Müller Externer Inhalt (IPMB, Department of Functional Genomics) studying the synaptic role of the APP gene family and their processing products in transgenic animal models.  Adobe  posted 02.2017

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Contact

Managing Director:
Prof. Dr. Hilmar Bading
IZN-Neurobiology, University of Heidelberg
Im Neuenheimer Feld 364
D-69120 Heidelberg, Germany

Phone:  +49 - 6221 - 54 8218
Fax:  +49 - 6221 - 54 6700
email:  Bading@nbio.uni-heidelberg.de

 

Coordinator:
Dr. Otto Bräunling
IZN-Neurobiology, University of Heidelberg
Im Neuenheimer Feld 364, 1.OG
D-69120 Heidelberg, Germany

Phone:  +49 - 6221 - 54 8694, 56 39007
Fax:  +49 - 6221 - 54 6700
email:  Braeunling@nbio.uni-heidelberg.de

 

Administration & Information:
Irmela Meng
IZN-Neurobiology, University of Heidelberg
Im Neuenheimer Feld 364, 1.OG
D-69120 Heidelberg, Germany

Phone:  +49 - 6221 - 54 8219
Fax:  +49 - 6221 - 54 6700
email:  Sekretariat@nbio.uni-heidelberg.de
Editor: Webmaster
Latest Revision: 2017-11-13
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