Leibniz Graduate School

The Leibniz Graduate School (LGS) SynaptoGenetics focuses on the genetics of synaptic functions and dysfunctions. 

 

The human brain is the most complex organ where about one hundred billion neurons and a similar number of glial cells form trillions of specialized cellular connections, the synapses. Synapses are dynamic structures, enabling the brain to establish various modes of performance, from simple regulatory activity to learning, memory and cognition. Recent developments in genetics and molecular biology allowed pivotal contributions to understanding synaptic function and dysfunctions (so-called synaptopathies), for instance by analyzing synaptic networks or by using distinct models for neuropathological diseases. Especially, sophisticated cell-specific genetic approaches in both the fruit fly Drosophila and the mouse enable the in-depth analysis of synaptic functions. In addition, modern human genetics in combination with next-generation sequencing techniques has revealed many potential disease-related genes. With this versatile toolbox the LGS on SynaptoGenetics aims at deciphering complex mechanisms of synaptic function and dysfunction.

 

The LGS on SynaptoGenetics pursues joint-effort research on synaptic function and pathological dysfunction bringing together expertise from human, mouse and Drosophila genetics and cutting-edge molecular biology techniques.

 

The LGS SynaptoGenetics is an initiative of the Leibniz Institute for Neurobiology (LIN) and the Medical Faculty and the Faculty for Natural Sciences of the Otto von Guericke University (OvGU) offering eight full-time PhD positions to highly motivated students of the life sciences. Moreover, several Master stipends are available. Currently, all PhD positions are filled. Graduate students performing research in the field of synaptogenetics can be associated with the LGS on request. 

 

The school is integrated in the graduate programs of the LIN and the OvGU.

 

News 

 

February 24-25, 2014

2nd LGS retreat meeting, Weimar Germany

 

May 17, 2014

"Lange Nacht der Wissenschaft", Magdeburg, Germany

Cooperation partners 

ovgugradschoolNPlast: Marie Curie Initial Training Network (external link)SFB854: Molecular Organisation of  Cellular Communication in the Immune System (external link)GRK1167: Cell-Cell-Communication in Neural and Immune Systems (external link)sfbtr31SFB779: Neurobiology of  motivated behaviorSFB TR62: Companion Technologyleibnizgemeinschaftlndw

Imprint

Leibniz-Institut für Neurobiologie (LIN)

Stiftung des Öffentlichen Rechts 
Brenneckestraße 6
D-39118 Magdeburg
Phone: +49-391-6263-92411 
Telefax: +49-391-6263-92419 
E-Mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Internet: http://www.ifn-magdeburg.de

Das Leibniz-Institut für Neurobiologie ist eine Stiftung des Öffentlichen Rechts

Vertretungsberechtigter Vorstand:
Eckart Gundelfinger (Geschäftsführender Direktor)
Thekla Thiel (Administrative Direktorin)

Zuständige Aufsichtsbehörde:
Kultusministerium des Landes Sachsen-Anhalt

Inhaltlich Verantwortlicher gemäß §5 TMG:
Constanze Seidenbecher


Wissenschaftsorganisation und Public Relations
(Anschrift wie oben)
Phone.: +49-391-6263-92401
E-Mail.: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

 

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Design & Programming

toolboxx-design Magdeburg
www.toolboxx.de

 

Pictures

alenah - fotolia.com
buchanon - dreamstime.com

Adriana Barmann

Adriana
Barmann

Sangamitra Boppudi

Sangamitra
Boppudi 

 Dijana Dobrota

Dijana
Dobrota

Ines Erdmann

Ines
Erdmann
 

Eve Gerecke

Eve
Gerecke

Iris Mueller

Iris
Müller

Sabrina Mueller

Sabrina
Müller 

Judith Camats Perna

Judith
Camats Perna

franziska altmueller

Franziska 
Altmüller, 
associated member

anil annamneedi

Anil
Annamneedi, 
associated member

Julia Abele

Julia
Abele,
associated member


 Adriana Barmann

 

My Photos Statement  

 

Adriana Barman

 

Project:

TP2 - Imaginggenetics of cognitivefunctions
Description

Supervisor: 

PD Dr. Constanze Seidenbecher,  Dr. Dr. Björn Schott
 

LIN:
 

Department:

Leibniz Institute of Neurobiology (LIN)
 

ImagingGenetics
  

Address:

 

Brenneckestr. 6, 39118 Magdeburg

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Diploma:

2001-2007 Title: Finanzielle Anreize und Gruppenleistung in computergestützten Gruppen

University: Georg-August-University of Göttingen

 

 Sangamitra Boppudi

 

My Photos Statement  

 

Sangamitra Boppudi

 

Project:

 

TP1 - Ras-MAPK signalling and cognitive function - The significance of activating mutations in human mental retardation
Description

 

Supervisor: 

 

Prof. Dr. med. Martin Zenker & PD Dr. rer. nat. Ilse Wieland

 

Faculty(OvGU):
 

Institute(OvGU):

 

Faculty of Medicine (FME) / University Medical Center (UKMD)
  

Institute of Human Genetics (IHG)

 

Address:

 

Leipziger Str. 44, 39120 Magdeburg
house 01

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MSc:

 

2009-2012 Mutation screening of new candidate genes for mental retardation by next generation sequencing (Prof. Dr. med. Martin Zenker) Integrative Neuroscience

Otto Von Guericke University, Magdeburg

 

BSc:

2004-2007 Genotyping of short tandem repeats of genomic
DNA isolated from swabs and stains of sexual assault cases. (Dr. N. Venkanna) Biotechnology, Microbiolgy, Chemistry

Andhra University, Visakhapatnam

 Dijana Dobrota

 

My Photos Statement  

 

Dijana Dobrota

 

Project:

 

TP5 - Interaction between amyloid-β protein and BDNF signaling in hippocampal neurogenesis
Description

 

Supervisor: 

 

Tanja Brigadski & Volkmar Leßmann

 

Faculty(OvGU):

 
Institute(OvGU):

 

Faculty of Medicine (FME) / University Medical Center (UKMD)
 

Institute of Physiology
 
 

Address:

 

Leipziger Str. 44, 39120 Magdeburg

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Diploma Thesis:

 

2011: Primary glial cell culture (Prof. Dr. Lidija Radenović & Prof. Dr. Pavle Anđus)

The centre for laser microscopy, University of Belgrade

 Ines Erdmann

 

My Photos Statement  

 

Ines Erdmann

 

Project:

TP7 - The role of neuron-glia communication during synaptogenesis in Drosophila melanogaster: Cell-specific proteome dynamics usig transgenic cell-selective click chemistry
Description

Supervisor:  

Prof. Dr. Daniela C. Dieterich

LIN:
 

Department(LIN)
Institute(OvGU):

Leibniz Institute of Neurobiology (LIN)
 
Neuralomics/Neurale Plastizität und Kommunikation
Institute of Pharmacology and Toxicology IPT (OvGU)
 
 

Address:


Brenneckestr. 6, 39118 Magdeburg /
Leipziger Str. 44, 39120 Magdeburg

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MSc:


2009-2010 Establishment und implementation of metabolic labeling of proteins in Drosophila melanogaster

Otto-von-Guericke University Magdeburg

BSc:


Das Verhältnis des Zapfen-Müllerzell-Verhältnisses in der Retina eines tag- und eines nachtaktiven Tieres

University Hamburg

 Eve Gerecke

 

My Photos Statement  

 

Eve Gerecke

 

Project:

 

TP8 - The control of synaptic stabilization and destabilization by scaffold and adhesion molecules in Drosophila
Description

 

Supervisor: 

 

Dr. Ulrich Thomas

 

LIN:
 

Department:

 

Leibniz Institute of Neurobiology (LIN)
 

Neurochemistry and Molecular Biology
 

Address:

 

Brenneckstr. 6, 39118 Magdeburg

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Diploma Thesis:

 

2011 Title: Flight Time Preferences and their Genetic Basis in Pollen Foragers and Drones of the Honey Bee (Apis mellifera L.)

University: Martin-Luther University Halle-Wittenberg

 

 Iris Mueller

 

My Photos Statement 

 

Iris Müller

 

Project:

 

TP4 - GABAergic mechanisms of fear conditioning
Description

 

Supervisor: 

 

Prof. Dr. Oliver Stork

 

LIN/Faculty(OvGU):
 

Department(LIN)/
Institute(OvGU):
 

Leibniz Institute of Neurobiology (LIN)
 

Department of Genetics and Molecular Neurobiology
Institute of Biology
 

Address:

 

Leipziger Str. 44, 39120 Magdeburg
house 91

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Diploma Thesis:

 

Behavioral screen of GAD65- and GAD67 haplodeficient mice in an animal model for posttraumatic stress disorder

 

 Sabrina Mueller

 

My Photos Statement  

 

Sabrina Müller

 

Project:

 

TP6 - Presynaptic maturation and Plasticity

Genetics of presynaptic scaffold proteins: Redundant and exclusive roles of Bassoon and Piccolo in synaptic assembly, function and plasticity.
Description

 

Supervisor: 
 

Dr. Anna Fejtova & Prof. Eckart D. Gundelfinger

LIN:
 

Department: 

Leibniz Institute of Neurobiology (LIN)
 

Neurochemistry & Molecular Biolog
 

Address:

 

Brenneckestr. 6, 39118 Magdeburg
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Programms:

 

2011 Leonardo DaVinci-Programm
The role of Netrin in the formation/differentiation of insulin-like peptide positive neurons in Drosophila melanogaster. (Prof. Dr. Angelika Stollewerk)
Queen Mary University of London
  

MSc:

2008-2010 Regeneration of the central nervous system of Drosophila melanogaster. (Prof. Dr. Reinhard Lakes-Harlan)
Justus-Liebig University of Gießen

BSc:

2005-2008 Study of diurnal activity pattern of giraffa camelopardalis in Frankfurt Zoo. (Prof. Dr. Wolfgang Clauss)
Justus-Liebig University of Gießen

 Judith Camats Perna

 

My Photos Statement  

 

Judith Camats Perna 

Project:

TP3 - Emotions, learning and memory: What roles does Grb2 play in hippocampal signalling?
Description

Supervisor: 
 

Prof. Mario Engelmann und Prof. Klaus Dieter Fischer

Institute(OvGU):
 

AG:
 

Institute für Biochemie und Zellbiologie 
 

AG Neuroendokrinologie & Verhalten

Address:

 

Leipziger Str. 44, 39120 Magdeburg
house 1

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MSc:

 

2010-2011 Regulation of the transcriptional coactivator CRTC1 in PS cDKO mice.
(Prof. Dr. Carles A. Saura Antolín)

Autonomous University of Barcelona (UAB)
 

BSc:

Chemokine signaling during axonal growth.
(Prof. Dr. Judit Herreros Danés)

University of Lleida (Udl)

 franziska altmueller

 

My Photos Statement  

 

Franziska Altmüller

 

associated member

 

 

Project:

 

Alterations of resting state plasticity through hyperactivation of the Ras-MAPK signaling pathway

Supervisor: 

Prof. Dr. med. Martin Zenker, Dr. Anna Fejtova, Dr. Ina Schanze, Dipl. MolMed Univ. Denny Schanze 

Institute:
 

Department:

 

Institute for Human Genetics / Leibniz Institute of Neurobiology (LIN)

 

Molecular Genetics / Neurochemistry & Presynaptic Plasticity

Address:

 

Leipziger Str. 44, 39120 Magdeburg / Brenneckestr. 6, 39118 Magdeburg

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 anil annamneedi

 

My Photos Statement  

 

Anil Annamneedi

 

associated member

 

Project:

 

Function of Bassoon in learning and memory processes

 

Supervisor: 

Prof. Dr. Eckart Gundelfinger, Prof. Dr. Oliver Stork



LIN:
 

Department:

 

Leibniz Institute For Neurobiology (LIN)
 

Department Neurochemistry and Molecular Biology


  

Address:

 

Brenneckestr. 6, 39118 Magdeburg

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MSc:

2007-2009 Master of Science
(Human Genetics) Andhra University, India

 

 

BSc:

2004-2007 Bachelor of Science
(Chemistry-Zoology-Biotechnology) Andhra University, India

 

 Julia Abele

 

My Photos Statement  

 

Julia Abele

 

Project:

Neuron-glia communication and contact rigidity: A molecular entry point to rejuvenate synaptic transmission?
 

Supervisor: 

Prof. Dr. Daniela C. Dieterich
 

LIN: Institute for Pharmakology and Toxicology
 

Department:

Neurale Plastizität und Kommunikation
 

Address:

 

Haus 20, Leipziger Str. 44, 39120 Magdeburg
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Associated: Yes
 

MSc 2011-2013:

Title: Integrative Neuroscience
University: Otto-von-Gericke University Magdeburg 
 

BSc 2008 - 2011:

 

Title: Biomedical Sciences
University: Phillips-University Marburg
 

Eckart D. Gundelfinger

Prof. Eckart D. Gundelfinger
 

PD Dr. Constanze I. Seidenbecher

PD Dr.  Constance I. Seidenbecher

Dr. Tanja Brigadski

Dr. Tanja Brigadski 

Prof. Daniela C. Dieterich

Prof. Daniela C. Dieterich

Prof. Mario Engelmann 

Prof. Mario Engelmann

Dr. Anna Fejitova

Dr. Anna Fejtova

Prof. Dr. Klaus-Dieter Fischer

Prof. Dr. Klaus-Dieter Fischer
 

Prof. Volkmar Leßmann

Prof. Volkmar Leßmann

Dr. Björn Schott

Dr. Björn Schott

Prof. Oliver Storck

Prof. Oliver Stork

Ulrich Thomas

PhD Ulrich Thomas

PD Ilse Wieland

PD Ilse Wieland

Prof. Martin Zenker 

Prof. Martin Zenker

 

 

 Eckart Gundelfinger

 

My Photos Statement 

 

Prof. Dr.


Eckart D. Gundelfinger

 

Headmaster of the Leibniz graduate school

Project:

 

RP6: Presynaptic maturation and Plasticity

LIN:
 

Leibniz Institute of Neurobiology (LIN) 

Department:
 

Neurochemistry & Molecular Biology

AG:
 

Chemical Synapses

Address:

 

Brenneckestr. 6, 39118 Magdeburg

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WWW:

http://www.lin-magdeburg.de/

 Constanze Seidenbecher

 

My Photos Statement 

 

PD Dr. Constanze I.


Seidenbecher  


 

Project:

 

Imaging genetics of cognitive functions 

LIN:
 
Department:
 
AG:
 

Leibniz Institute of Neurobiology (LIN)
 
Neurochemistry & Molecular Biology
  
Perisynaptic Extracellular Matrix
 
   

Address:

 

Brenneckestr. 6, 39118 Magdeburg

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WWW:

http://www.ifn-magdeburg.de/de/abteilungen/
neurochemie_molekularbiologie/ag_extrazell_matrix/index.jsp

 Tanja Brigadski

 

My Photos Statement 

 

Jun.-Prof.


Tanja Brigadski

 

Project:

 

Interaction between amyloid-β protein and      
BDNF signaling in hippocampal neurogenesis

 

Faculty (OvGU):

 
Institute (OvGU):
 
AG:

 

Faculty of Medicine (FME) / University Medical Center (UKMD)
 
Institute of Physiology (IPHY)
 
Synaptic Plasticity
 

Address:

 

Leipziger Str. 44, 39120 Magdeburg


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 Daniela Dieterich

 

My Photos Statement 

 

Prof. Dr.


Daniela C. Dieterich

 

Project:

 

The role of neuron-glia communication during synaptogenesis in Drosophila melanogaster: Cell-specific proteome dynamics usig transgenic cell-selective click chemistry

 

Faculty (OvGU):

 
Institute (OvGU):

 

Faculty of Medicine (FME) / University Medical Center (UKMD)
 
Institute of Pharmacology and Toxicology IPT (OvGU)
 

Address:

 

Leipziger Str. 44, 39120 Magdeburg /
Brennecke Str. 6, 39118 Magdeburg


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 leer

 

My Photos Statement 

 

Prof. Dr. 


Mario Engelmann

 

Project:

 

TP3: Emotions, learning and memory: What roles does Grb2 play in hippocampal signalling?

 

Faculty (OvGU):

Faculty of Medicine (FME) / University Medical Center (UKMD)

 

Institute (OvGU):

 

Institutes of Biochemistry and Cellbiology (IBZ)

Address:

 

Leipziger Str. 44, 39120 Magdeburg

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 Anna Fejitova

 

My Photos Statement 

 

Dr. Anna Fejtová

 

Project:

 

TP6 : Presynaptic maturation and Plasticity

Genetics of presynaptic scaffold proteins: Redundant and exclusive roles of Bassoon and Piccolo in synaptic assembly, function and plasticity

 

LIN:
 

Leibniz Institute of Neurobiology (LIN)

Department:
 

Neurochemistry & Molecular Biology

AG:
 
 

Chemical Synapses

Address:

 

Brenneckestr. 6, 39118 Magdeburg
 
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 Prof. Dr. Klaus-Dieter Fischer

 

My Photos Statement 

 

Prof. Dr. 


Klaus-Dieter Fischer

 

Project:

 

TP3: Emotions, learning and memory: What roles does Grb2 play in hippocampal signalling?

 

Department (OvGU):

Faculty of Medicine (FME)

Institute (OvGU):

Institutes of Biochemistry and Cellbiology (IBZ)

Address:

 

Leipziger Str. 44, 39120 Magdeburg

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 Volkmar Lessmann

 

My Photos Statement 

 

Prof. Volkmar Leßmann

 

Project:

 

Interaction between amyloid-β protein and      
BDNF signaling in hippocampal neurogenesis

 

Faculty (OvGU):

Faculty of Medicine (FME) / University Medical Center (UKMD)
 

Institute (OvGU):
 

Institute of Physiology (IPHY)

AG:
 

Synaptic Plasticity

Address:

 

Leipziger Str. 44, 39120 Magdeburg


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 Bjoern Schott

 

My Photos Statement 

 

Dr. Dr. Björn H. Schott

 

Project:

 

Imaging genetics of cognitive functions

 

LIN:
 

Leibniz Institute of Neurobiology (LIN)

Department:
 
 

Behavioral Neurology

Address:

 

Brenneckestr. 6, 39118 Magdeburg
 
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Department 2 / 
Institute 2:

Psychiatry and Psychotherapy
Charité University Hospital

Address 2:

Charitéplatz 1, 10117 Berlin

WWW:

http://psy-ccm.charite.de/

 Oliver Storck

 

My Photos Statement 

 

Prof. Dr. Oliver Stork

 

Project:

 

GABAergic mechanisms of fear conditioning

 

Faculty (OvGU):
 

Faculty of Natural Sciences (FNW)

Institute (OvGU):
  

Institute of Biology

AG:
 

Genetics and Molecular Neurobiology

Address:

 

Leipziger Str. 44, house 91
 
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 Ulrich Thomas

 

My Photos Statement 

 

Ulrich Thomas, PhD

 

Project:

 

T8: The control of synaptic stabilization and destabilization by scaffold and adhesion molecules in Drosophila

 

LIN:
 

Leibniz Institute of Neurobiology (LIN)

Department:
 

Neurochemistry & Molecular Biology

AG:
 

Functional Genetics of the Synapse

Address:

 

Brenneckestr. 6, 39118 Magdeburg
 
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 Ilse Wieland

 

My Photos Statement 

 

PD Dr. rer. nat. 


Ilse Wieland

 

Project:

 

Ras-MAPK signalling and cognitive function - The significance of activating mutations in human mental retardation

 

Faculty (OvGU):
 

Faculty of Medicine (FME) / University Medical Center (UKMD)

Institute (OvGU):
 

Institute of Human Genetics (IHG)

AG:
 

Molecular Genetics 

Address:

 

Leipzigerstr. 44, Haus 01


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  leer

My Photos Statement 

 

Prof. Dr. med.  


Martin Zenker

 

Project:

 

Ras-MAPK signalling and cognitive function - The significance of activating mutations in human mental retardation

 

Faculty (OvGU):
 

Faculty of Medicine (FME) / University Medical Center (UKMD)

Institute (OvGU):
 

Institute of Human Genetics (IHG)

Address:

 

Leipzigerstr. 44, Haus 01


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LGS logo

 

 

leer

Zdenka
Červenková

deniz madencioglu

Deniz Ashan
Madencioglu

Rebecca Poetschke

Rebecca
Pötschke

marieke klein

Marieke

Klein

Alexandra Spuhn

Alexandra
Spuhn

leer

Syed
Ahsan Raza

leer

Jan
Teuber

leer

Carina
Fürst

Anne Assmann

Anne 
Assmann, 
associated member

leer

Paula
Säring

 

 leer

 

 

 

Zdenka Červenková

Project:

 

Supervisor: 



Department:

 

Neurochemistry and Molecular Biology
Leibniz Institute for Neurobiology
 

Address:

 

Brenneckstr. 6, 39118 Magdeburg

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BSc:

 


 

 deniz madencioglu

 

 

 

Deniz

Madencioglu

 

MSc Thesis:

Determining a behavioural phenotype and brain morphology of Ndr2 knockout mice

Associated:

Yes

Year:

2012

Supervisor: 

Prof. Dr. Oliver Stork

Department:

 

Molecular Neurobiology and Genetics

Institute:

 

Institute of Biology

Current Position:

PhD Student

E-mail:

 

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 Rebecca Poetschke

 

 

 

Rebecca Pötschke 

Project:

Extracellular tagging of the Voltage-gated potassium channel hKv1.3 for Assessment of its surface mobility in living T cells

Supervisor: 

Ulrich Thomas, PhD

Department:

 

Neurochemistry and Molecular Biology
Leibniz Institute for Neurobiology
 

Address:

 

Brenneckstr. 6, 39118 Magdeburg

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BSc:

 

2010 Modelling of the CoCoME in Vericap –
Study of a testing protocol in component-based Software Systems

Martin-Luther Universität Halle

 

 marieke klein  

 

 

MSc Marieke Klein

 

Email contact:

 

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MSc:

Neuroscience
2011 - 2012
OvGU/LIN

"fMRI study to investigate the effect of polymorphisms on episodic memory"
(Dr. Björn H. Schott & PD Dr. Constanze I. Seidenbecher)

 

BSc: 

 

The effect of BDNF and serotonin receptor 2A polymorphisms on neural mechanisms of memory formation in humans (Prof. Dr. Gerard Martens)

University: Radboud University Nijmegen, The Netherlands

 

 Alexandra Spuhn  

 

 

MSc Alexandra Spuhn

 

Email contact:

 

not announced

MSc:

Neuroscience
2011 - 2012
OvGU/LIN
"Local micromanipulation of cells using microfluidics"
(Prof. Dr. Daniela C. Dieterich)

 

BSc: 

 

Biology
2007-2010
TU Braunschweig
Theme: LIM-Kinase 1-abhängige Phosphorylierung von Cofilin-1:
Analyse der neuronalen Morphologie.

 

 leer

 

 

Syed Ahsan Raza

 

Msc Thesis:

Epigenetics and Analysis of GABAergic Interneurons in Fear Memory
 

Associated:

No
 

Year:

2011
 

Supervisor:

Prof. Dr. Oliver Stork
 

Department:

Molecular Neurobiology and Genetics
 

Institute:

Institute of Biology
 

Current Position:

PhD Student
 

E-mail:

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 leer

 

 

Jan Teuber

 

MD Thesis: The ubiquitin ligase Praja1 and its role in neuronal differentiation

Associated: Yes

Year: 2013

Supervisor:

Prof. Dr. Oliver Stork

Department:

Molecular Neurobiology and Genetics

Institute:

Institute of Biology

Current Position:

PhD Student

E-mail:

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 Anne Assmann

 

 

 

Anne Assmann

 

associated member

 

Project:

 

Influence of depression risk alleles on learning and memory function

 

Supervisor: 

Dr. Dr. Björn Schott, PD Dr. Constanze Seidenbecher

LIN:
 

Department:

 

Leibniz Institute of Neurobiology (LIN)
 

Behavioural Neurology
  

Address:

 

Brenneckestr. 6, 39118 Magdeburg

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 Carina Fürst 

 

 

Carina Fürst

 

MSc Thesis:

Mobility analysis of the low-voltage-activated T-type calcium channel Cav3.2 in dorsal root ganglion neurons

Year:  2014

Supervisor:

Dr. Ulrich Thomas/ Dr. Martin Heine

Department: Neurochemistry

Institute:

Leibniz Institute for Neurobiology

 Paula Säring

 

 

 

Paula Säring

 

MSc Thesis:

Functional Characterization of the Immunoproteasome Subunit LMP7 in the Mammalian Brain

Associated:

no

Year:

2013

Supervisor: 

Prof. Dr. Daniela Dieterich

Department:

Neural Plasticity and Communication
 

Institute:

Institute for Pharmacology and Toxicology
 

Current Position:
 

PhD Student

E-mail:
 

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Men BoxTP 1

 

 

Ras-MAPK signalling and cognitive function -
The significance of activating mutations in human mental retardation.

 

Prof. Martin Zenker

 

 

Activating germline mutations in various genes encoding components or modulators of the Ras-MAPK signalling pathway have been found to cause a group of clinically overlapping syndromes (including Noonan, CFC and Costello syndrome). Cognitive deficits of variable expression are part of all these diseases and are considered to reflect dysregulated Ras-MAPK signalling in the nervous system. We hypothesize that mutations in other modulators of the pathway, that are preferentially expressed in neuronal cells, may be responsible for mental retardation without the typical physical symptoms of Noonan syndrome and related disorders. We therefore intend to screen the genes for neuronal components / modulators of this pathway in a large cohort of patients with non-syndromic or non-specific mental retardation using new sequencing technologies. Sequence variants detected by this approach will be further validated and functionally evaluated. 

    Schubbert S, Zenker M, Rowe SL, Boll S, Klein C, Bollag G, van der Burgt I, Musante L, Kalscheuer V, Wehner LE, Nguyen H, West B, Zhang KY, Sistermans E, Rauch A, Niemeyer CM, Shannon K, Kratz CP (2006) Germline KRAS mutations cause Noonan syndrome. Nat Genet 38:331-336.

 

    Zenker M et al. (2007) SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. J Med Genet 44:651-656.

 

    Cirstea IC et al. (2010) A restricted spectrum of NRAS mutations causes Noonan syndrome. Nat Genet 42:27-29.

 

    Martinelli S et al. (2010) Heterozygous germline mutations in the CBL tumor-suppressor gene cause a Noonan syndrome-like phenotype. Am J Hum Genet 87:250-257.

Men BoxTP 2

 

 

Imaging Genetics of Cognitive Functions - Significance of the Ras-MAP kinase signalling pathway for cognitive functions - influence of genetic polymorphisms on learning processes in humans

 

Dr. Björn H. Schott & PD Dr. Constanze I. Seidenbecher

 

We want to study the influence of single nucleotide polymorphisms (SNP) in genes encoding molecules of the Ras signalling pathway on human learning and memory performance. A large cohort of approx. 700 healthy human subjects shall be studied in hippocampus- and striatum-dependent cognitive processes using neuropsychological testing and multimodal non-invasive brain imaging.  With fMRI measurements of the BOLD response we will elucidate the functional anatomy of these cognitive processes. The temporal dynamics shall be investigated with EEG. We will focus on candidate genes of the RAS pathway and, besides the SNPs, also look for copy number variations in these genes.

 

    Schott BH, Niehaus L, Wittmann BC, Schutze H, Seidenbecher CI, Heinze HJ, Duzel E (2007) Ageing and early-stage Parkinson's disease affect separable neural mechanisms of mesolimbic reward processing. Brain 130:2412-2424.

 

    Schott BH, Seidenbecher CI, Richter S, Wustenberg T, Debska-Vielhaber G, Schubert H, Heinze HJ, Richardson-Klavehn A, Duzel E (2011) Genetic variation of the serotonin 2a receptor affects hippocampal novelty processing in humans. PLoS One 6:e15984.

 

    Schott BH, Seidenbecher CI, Fenker DB, Lauer CJ, Bunzeck N, Bernstein HG, Tischmeyer W, Gundelfinger ED, Heinze HJ, Duzel E (2006) The dopaminergic midbrain participates in human episodic memory formation: evidence from genetic imaging. J Neurosci 26:1407-1417.

 

    Schott BH, Minuzzi L, Krebs RM, Elmenhorst D, Lang M, Winz OH, Seidenbecher CI, Coenen HH, Heinze HJ, Zilles K, Duzel E, Bauer A (2008) Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. J Neurosci 28:14311-14319.

Mouse BoxTP 3

 

 

Emotions, learning and memory: What roles does Grb2 play in hippocampal signalling?

 

Prof. Mario Engelmann & Prof. Klaus Dieter Fischer

 

 

Neurotrophins such as BDNF activate the Ras signalling cascade downstream of receptor tyrosine kinases and are critical to the induction of neuronal plasticity. Grb2 is an intracellular adaptor molecule that mediates Ras signalling upon receptor tyrosine kinase stimulation. We will study the relevance of Grb2 in the generation of emotions and to learning and memory using conditional Grb2 knockout mice. Manipulated mutant mice will be exposed to mild chronic stress and to the application of anti-depressants, both of which are known to trigger neurotrophin action resulting in neurogenesis and increased hippocampal plasticity.

 

    Noack J, Richter K, Laube G, Haghgoo HA, Veh RW, Engelmann M (2010) Different importance of the volatile and non-volatile fractions of an olfactory signature for individual social recognition in rats versus mice and short-term versus long-term memory. Neurobiol Learn Mem 94:568-575.

 

     Tobin VA, Hashimoto H, Wacker DW, Takayanagi Y, Langnaese K, Caquineau C, Noack J, Landgraf R, Onaka T, Leng G, Meddle SL, Engelmann M, Ludwig M (2010) An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 464:413-417.

 

    Zelena D, Langnaese K, Domokos A, Pinter O, Landgraf R, Makara GB, Engelmann M (2009) Vasopressin administration into the paraventricular nucleus normalizes plasma oxytocin and corticosterone levels in Brattleboro rats. Endocrinology 150:2791-2798.

 

    Missy K, Hu B, Schilling K, Harenberg A, Sakk V, Kuchenbecker K, Kutsche K, Fischer KD (2008) AlphaPIX Rho GTPase guanine nucleotide exchange factor regulates lymphocyte functions and antigen receptor signaling. Mol Cell Biol 28:3776-3789.

 

    Tedford K, Nitschke L, Girkontaite I, Charlesworth A, Chan G, Sakk V, Barbacid M, Fischer KD (2001) Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling. Nat Immunol 2:548-555.

mouse boxTP 4

 

 

GABAergic interneurons in fear conditioning: Role of synaptic GAD expression

 

Prof. Oliver Stork

 

Groups of GABAergic interneurons filter sensory input to the amygdala, determine its principle neuron excitability  and control network activity patterns involved in information processing. These cell populations mediate different aspects of the acquisition, consolidation, and extinciton of fear memories. In this project we will investigate the particular role of synaptic vs non-synaptic forms of the key enzyme of GABA synthesis, glutamic acid decarboxylase (GAD)65 and GAD67. Both enzymes are specifically expressed in amygdalar GABA interneurons, albeit at different levels in different subpopulations. Using constitutive and conditional mutant mice as well as lentiviral gene transfer we will locally inactivate GAD65 or GAD67 in selected GABAergic subpopulations and investigate the consequences for fear memory formation. Our findings can be expected to help understanding critical mechanisms of both physiological and pathological fear memory storage through the amygdala.

 

    Sangha S, Narayanan RT, Bergado-Acosta JR, Stork O, Seidenbecher T, Pape HC (2009) Deficiency of the 65 kDa isoform of glutamic acid decarboxylase impairs extinction of cued but not contextual fear memory. J Neurosci 29:15713-15720.

 

    Kluge C, Stoppel C, Szinyei C, Stork O, Pape HC (2008) Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity. Learn Mem 15:252-260.

 

    Bergado-Acosta JR, Sangha S, Narayanan RT, Obata K, Pape HC, Stork O (2008) Critical role of the 65-kDa isoform of glutamic acid decarboxylase in consolidation and generalization of Pavlovian fear memory. Learn Mem 15:163-171.

 

    Stork O, Yamanaka H, Stork S, Kume N, Obata K (2003) Altered conditioned fear behavior in glutamate decarboxylase 65 null mutant mice. Genes Brain Behav 2:65-70.

 

mouse boxTP 5

 

 

Interactions between amyloid b-protein and BDNF signalling in hippocampal neurogenesis in a genetic mouse model of Alzheimer‘s disease

 

Jun.-Prof. Tanja Brigadski & Prof. Volkmar Lessmann

 

A neuropathological characteristic of Alzheimer’s disease is the atropic change in the hippocampus, a brain region known to be important for formation of spatial memories. Despite the typical neurodegeneration during Alzheimer’s disease recent studies suggest an enhanced neurogenesis in the hippocampus of Alzheimer patients and genetic mouse models of Alzheimer‘s disease which is accompanied by an incomplete neuronal differentiation of hippocampal neurons. While the increased proliferation is supposed to be mediated by the amyloid b-protein, which is a central protein in the pathogenesis of Alzheimer’s disease, the incomplete neuronal differentiation could be mediated by a lack of the neurotrophic factor BDNF.

 

This project will analyse the interaction between amyloid b-protein and BDNF signalling during hippocampal neurogenesis. The project will involve confocal microscopy, electrophysiology, cell biology and molecular biology techniques, to analyse the consequences of altered amyloid b-protein and BDNF-levels in generation and maturation of hippocampal neurons.

    Brigadski T, Hartmann M, Lessmann V (2005) Differential vesicular targeting and time course of synaptic secretion of the mammalian neurotrophins. J Neurosci 25:7601-7614.

 

    Kolarow R, Brigadski T, Lessmann V (2007) Postsynaptic secretion of BDNF and NT-3 from hippocampal neurons depends on calcium calmodulin kinase II signaling and proceeds via delayed fusion pore opening. J Neurosci 27:10350-10364.

 

    Lessmann V, Brigadski T (2009) Mechanisms, locations, and kinetics of synaptic BDNF secretion: an update. Neurosci Res 65:11-22.

mouse boxTP 6

 

 

Genetics of presynaptic scaffold proteins: Redundant and exclusive roles of Bassoon and Piccolo in synaptic assembly, function and plasticity

 

Dr. Anna Fejtová & Prof. Eckart D. Gundelfinger

 

Bassoon und Piccolo are presynaptic scaffold proteins controlling synapse assembly, maturation, stability and function. They share a high sequence homology, which is mirrored in a number of common interaction partners, and highly overlapping subcellular localization patterns. The fact that animals lacking both Bassoon and Piccolo are in contrast to single mutants not viable also suggests the functional redundancy of these two proteins. However, we recently identified a number of cellular processes (e.g. axonal vesicle transport, neuronal morphogenesis, dispersion of vesicles during synaptic activity and modulation of neuronal activity at systemic level), where Bassoon or Piccolo have an exclusive function. The molecular basis of this functional redundancy and exclusivity is absolutely unclear up to date and its elucidation is the main goal of our project.

    Hallermann S, Fejtová A, Schmidt H, Weyhersmuller A, Silver RA, Gundelfinger ED, Eilers J (2010) Bassoon speeds vesicle reloading at a central excitatory synapse. Neuron 68:710-723.

 

    Fejtová A, Davydova D, Bischof F, Lazarevic V, Altrock WD, Romorini S, Schone C, Zuschratter W, Kreutz MR, Garner CC, Ziv NE, Gundelfinger ED (2009) Dynein light chain regulates axonal trafficking and synaptic levels of Bassoon. J Cell Biol 185:341-355.

 

    Ghiglieri V, Picconi B, Sgobio C, Bagetta V, Barone I, Paille V, Di Filippo M, Polli F, Gardoni F, Altrock W, Gundelfinger ED, De Sarro G, Bernardi G, Ammassari-Teule M, Di Luca M, Calabresi P (2009) Epilepsy-induced abnormal striatal plasticity in Bassoon mutant mice. Eur J Neurosci 29:1979-1993.

 

    Leal-Ortiz S, Waites CL, Terry-Lorenzo R, Zamorano P, Gundelfinger ED, Garner CC (2008) Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis. J Cell Biol 181:831-846.

fruitfly boxTP 7

 

The role of neuron-glia communication during synaptogenesis in Drosophila melanogaster: Cell-specific proteome dynamics using transgenic cell-select click chemistry

 

Dr. Daniela C. Dieterich

 

The emerging concept of the “Tripartite synapse” points to the importance of glia cells for neuronal function and development. Although it is well established that astrocytes are important for the formation and maintenance of synaptic contacts, sense neuronal activity and actively participate in homeostatic scaling, it is unclear if the astroglial proteome is as dynamic as the neuronal. In this project we aim to decipher the communication of neurons with astrocytes at the synaptic level in Drosophila larvae and adult flies using cell-selective labeling of newly synthesized priteins via click chemistry. In more detail we ask the following questions: Do characteristic signature proteomes for different stages during development of the neuromascular junction exist in neurons, in muscle cells and also in glia cells? Where in the cell are these proteins synthesized – only in the cell somata or also locally in cellular processes? Do glial cells react as dynamic as neurons to changes in the neuronal activity pattern?

 

    Dieterich DC, Link AJ, Graumann J, Tirrell DA, Schuman EM (2006) Selective identification of newly synthesized proteins in mammalian cells using bioorthogonal noncanonical amino acid tagging (BONCAT). Proc Natl Acad Sci U S A 103:9482-9487.

 

    Dieterich DC, Lee JJ, Link AJ, Graumann J, Tirrell DA, Schuman EM (2007) Labeling, detection and identification of newly synthesized proteomes with bioorthogonal non-canonical amino-acid tagging. Nat Protoc 2:532-540.

 

    Dieterich DC, Hodas JJ, Gouzer G, Shadrin IY, Ngo JT, Triller A, Tirrell DA, Schuman EM (2010) In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat Neurosci 13:897-905.

 

    Ngo JT, Champion JA, Mahdavi A, Tanrikulu IC, Beatty KE, Connor RE, Yoo TH, Dieterich DC, Schuman EM, Tirrell DA (2009) Cell-selective metabolic labeling of proteins. Nat Chem Biol 5:715-717.

fruitfly boxTP 8

 

The control of synaptic stabilization and destabilization by scaffold and adhesion molecules in Drosophila

 

Dr. Ulrich Thomas

 

 

Synapse remodeling involves the well-controlled destabilization of synaptic protein complexes balanced by stabilizing mechansims, which warrant the maintenance of synaptic connectivity. Disrupting this balance interferes with the striking capacity of neural networks to undergo use-dependent adjustments at the level of synaptic junctions. In fact, mental disorders such as autism and some forms of neural degeneration may result from such disturbancies. Our recent studies imply, that the highly conserved Dlg-scaffold protein complex controls the stability of glutamatergic neuromuscular junctions in Drosophila,possibly through interactions with synaptic cell adhesion molecules (CAMs) such as Neurexin and Neuroligin-1. Based on the versatility of Drosophila genetics, this project is aimed at deciphering the regulation and dynamics of the Dlg complex and associated cell adhesion complexes in controlling synaptic stability under various conditions (e.g. during activity-induced synaptic terminal growth). A broad range of methods including classical and molecular genetics, confocal microscopy and life imaging techniques will be employed.

 

    Thomas U, Kobler O, Gundelfinger ED (2010) The Drosophila larval neuromuscular junction as a model for scaffold complexes at glutamatergic synapses: benefits and limitations. J Neurogenet 24:109-119.

 

    Bachmann A, Kobler O, Kittel RJ, Wichmann C, Sierralta J, Sigrist SJ, Gundelfinger ED, Knust E, Thomas U (2010) A perisynaptic menage a trois between Dlg, DLin-7, and Metro controls proper organization of Drosophila synaptic junctions. J Neurosci 30:5811-5824.

 

    Mendoza-Topaz C, Urra F, Barria R, Albornoz V, Ugalde D, Thomas U, Gundelfinger ED, Delgado R, Kukuljan M, Sanxaridis PD, Tsunoda S, Ceriani MF, Budnik V, Sierralta J (2008) DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function. J Neurosci 28:304-314.

 

    Bachmann A, Timmer M, Sierralta J, Pietrini G, Gundelfinger ED, Knust E, Thomas U (2004) Cell type-specific recruitment of Drosophila Lin-7 to distinct MAGUK-based protein complexes defines novel roles for Sdt and Dlg-S97. J Cell Sci 117:1899-1909.

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