Header Wanker Lab

E. Wanker Lab

Proteomics and Molecular Mechanisms of Neurodegenerative Diseases

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Jan 26, 2021: PhD recruitment round for spring 2021 - we are activated! (Due to an error, we weren't.)

Please check out our lab's project:

"How do proteins that interact with mutated huntingtin affect its abundance? A study of Huntington’s disease in cell models and neurons of Drosophila melanogaster"
Huntington’s disease (HD) is a fatal neurodegenerative disease with progressive loss of motor, cognitive and language abilities, leading to premature death after years of severe suffering. As a neurodegenerative protein misfolding disease, HD is related to Alzheimer’s and Parkinson’s disease, as a rare polyglutamine disease to Kennedy’s disease and the spinocerebellar ataxias.
Misfolding and aggregation of the mutant huntingtin protein with an elongated polyglutamine stretch is at the root of the disease.

Confocal microscopy image of a Drosophila brain in which expression of huntingtin with an elongated polyglutamine sequence was turned on for 6 days and turned off for the 18 days that followed. Red: synapses present in all neuronal cells. Green: huntingtin aggregates that form and deposit in the brain.

We have established HD fly models that enable the investigation of huntingtin proteins, their aggregation and seeding specifically in neurons, in vivo. See: Anne Ast et al. “mHTT Seeding Activity: A Marker of Disease Progression and Neurotoxicity in Models of Huntington's Disease”. Molecular Cell. 2018 Sep 6;71(5):675-688.e6. https://doi.org/10.1016/j.molcel.2018.07.032.*

Also, we have developed technologies that enable the quantitative detection of protein-protein interactions (PPIs) in mammalian cells, like our recent LuTHY assay. See: Trepte et al. “LuTHy: A Double-Readout Bioluminescence-Based Two-Hybrid Technology for Quantitative Mapping of Protein-Protein Interactions in Mammalian Cells.” Molecular Systems Biology. 2018 Jul 11;14(7):e8071. https://doi.org/10.15252/msb.20178071.*

In high-throughput screenings using these technologies, we have recently identified various proteins that interact with wild-type and mutant huntingtin in cell models. Among them, ubiquitin protein ligases (UBLs) and deubiquitinating enzymes (DUBs) are of particular interest to us, because they are known to regulate the degradation of other proteins in mammalian cells.
We are now looking for a PhD candidate to join our team to help elucidate the molecular mechanisms that control wild-type and mutant huntingtin protein levels. Specifically, the project will investigate the influence of E3 ligases and DUBs on the abundance of
wild-type and mutant huntingtin in cell models and in HD transgenic flies.

Using the CRISPR/Cas9 technology on mammalian cells, we will generate cell lines that endogenously express huntingtin fusions, which are tagged with nanoluciferase or fluorescent proteins such mCitrine or mNeonGreen. These cell lines will be used to determine the huntingtin dynamics but also to validate huntingtin-interacting UBL and DUB proteins.

Moreover, through knockdown and overexpression of selected ubiquitin and DUB proteins, e.g., the E3 ligase UBR5, we will assess whether the degradation of mutant huntingtin can be promoted. To this end, we want to determine whether the ubiquitin proteasome system (UPS) or autophagy are predominantly responsible for mutant huntingtin degradation in cells. Furthermore, HD transgenic flies will be used to investigate whether huntingtin degradation in non-dividing post-mitotic neurons is different from fast-dividing non-neuronal cells. Altogether, this work will bring significant contributions to finding a new huntingtin lowering strategy, which is one of the most promising current approaches in the search of treatments for Huntington’s disease.

Become a member of a highly motivated, fun and collaborative team full of ideas. As part of our team you will learn, use and develop a set of sophisticated biochemical, biophysical, cellular, genetic, proteomic, imaging and fly techniques to make a significant contribution towards the elucidation and future therapy of Huntington’s disease.

Our group has been active in protein misfolding disorders and interactomics for many years and has made several pioneering discoveries: The identification of protein aggregation in Huntington’s disease (Scherzinger et al. Cell, 1997), the generation of the first genome-wide protein-protein interaction network (Stelzl et al. Cell, 2005) or the effect of small molecules on misfolded protein species relevant to disease (Ehrnhoefer et al. Nature Structural and Molecular Biology, 2006; Bieschke et al.
Nature Chemical Biology, 2011).

* For a more general review of the significance of Ast et al., see:
https://www.mdc-berlin.de/news/press/predicting-onset-and-course-huntingtons-disease
* For commentary on Trepte et al., see:
https://www.embopress.org/doi/full/10.15252/msb.20188485
https://www.mdc-berlin.de/news/news/two-experiments-one-fell-swoop

Looking forward to meeting enthusiastic candidates!

About our research:

Millions of people worldwide suffer from neurodegenerative disorders, like Alzheimer’s, Parkinson’s or Huntington’s disease. Most of these illnesses break out later in life. Correlated to the current demographic shift towards aging societies in many countries, the number of people affected with neurodegenerative diseases is growing.

Still, we do not understand exactly how neurodegenerative diseases develop. One of the characteristic features many neurodegenerative diseases share is the deposition of abnormally folded proteins in patient brains.

My group's research focusses on ‘Neuroproteomics’, the protein-based investigation of neurodegenerative diseases. We aim to elucidate the molecular principles by which proteins, sometimes abnormally folded, alone or in interaction, lead to cellular toxicity and neuronal dysfunction, causing neurodegeneration.

We pursue two main lines of investigation: Hypothesis-driven molecular studies of protein misfolding, aggregation and spreading, on the one hand, unbiased protein-protein interaction or ‘interactomics’ studies on the other. Click "Research" above to read about our current projects and fields of interest.

 

Team

Erich Wanker, PhD, DI

Principal Investigator

+49/30/9406-2157
ewanker@mdc-berlin.de

 

Anne Ast, PhD

Postdoc

+49/30/9406-2636
anne.ast@mdc-berlin.de

 

Irem Bayraktaroglu, BSc

Master's student

+49/30/9406-3481
irem.bayraktaroglu@mdc-berlin.de

 

Stephanie Beetz, MSc

Technician

+49/30/9406-2353
stephanie.beetz@mdc-berlin.de

 

Annett Böddrich, PhD

Senior scientist, project manager

+49/30/9406-2357
a.boeddrich@mdc-berlin.de

 

Megan Bonsor, MSc

Graduate student

+49/30/9406-3421
megan.bonsor@mdc-berlin.de

 

Lydia Brusendorf, DI

Technician

+49/30/9406-2636
lydia.brusendorf@mdc-berlin.de

 

Annika Deckert, PhD

Postdoc, Alzheimer's Association Research Fellow

+49/30/9489-2147
annika.deckert@mdc-berlin.de

 

Marta Dominguez Martinez, MSc

Graduate student

+49/30/9489-2147
marta.dominguez@mdc-berlin.de

 

Jana Erlmoser

Undergraduate student

+49/30/9406-2805
jana.erlmoser@mdc-berlin.de

 

Sabrina Golusik, BTA

Technician

+49/30/9406-2805
sabrina.golusik@mdc-berlin.de

 

Christian Hänig, DI

Computational scientist, IT, automation

+49/30/9406-2437
c.haenig@mdc-berlin.de

 

Sarina Hilke

Technician

+49/30/9406-3481
sarina.hilke@mdc-berlin.de

 

Simona Kostova, MSc

Graduate student

+49/30/9406-2433
simona.kostova@mdc-berlin.de

 

Mara Liebich

Technician

+49/30/9406-2433
mara.liebich@mdc-berlin.de

 

Adrian Marti Pastor

Undergraduate student

+49/30/9406-3481
adrian.martipastor@mdc-berlin.de

 

Nancy Neuendorf, BTA

Senior technician

+49/30/9406-2805
nancy.neuendorf@mdc-berlin.de

 

Eduardo Silva Ramos, PhD

Postdoc

+49/30/9489-2138
eduardo.silvaramos@mdc-berlin.de

 

Sigrid Schnögl, MPhil, MBA

Coordinator

+49/30/9406-2357
sigrid.schnoegl@mdc-berlin.de

 

Christopher Secker, Dr. med.

Postdoc

+49/30/9406-2433
christopher.secker@mdc-berlin.de

 

Martina Zenkner, DI

Senior technician, lab manager

+49/30/9406-2357
zenkner@mdc-berlin.de

 

 

> Previous members <

Claudia Abraham

Mohammed Ahmed

Anna-Clara Amler

Kathrin Andrich, PhD

Iris Apostel-Krause

Anup Arumughan, PhD

Vinayagam Arunachalam, PhD

Jennifer Doreen Augsten

Katrin Bagola

Bianca Bauer

Lynn van der Beek

Simon Berberich

Annaporna Bhat

Jan Bieschke, PhD

Malla Bimalla

Nicole Bock

Svenja Bolz

Anne Borowski

Lamia Bouguerne

Nisrin Nora Boukantar

Yacine Bounab, PhD

Anja Briese

Raul Bukowiecki

Alexander Buntru, PhD

Anne Busch, PhD

Branca Cajavec

Morena Cauglia

Irene Carod

Laura Benitez Casanova

Gautam Chaurasia, PhD

Ummi Hadiba Ciptasari

Louica Delius

Monishita Dey

Ina Dieckmann

Nea Dierolf

Lisa Diez, PhD

Franziska Dinter

Christin Donner

Ulrike Drewes

Anja Dröge, PhD

Juliane Edel, Master

Dagmar Ehrnhöfer, PhD

Thomas Ehrnhöfer

Sabine Engemann, PhD

Figen Ertas

Claudia Eulenberg

Maik Faltysek

Claudia Felsch

Christian Fink, PhD

Carina Fischer, MSc

Leonhard Fister

Alexandra-Iona Forrai

Raphaele Foulle

Ralf Friedrich, PhD

Clemens Franke

Anja Fritzsche

Joris Geigenmüller, BSc

Klaus Genser, PhD

Heike Göhler, PhD

Gerlinde Grelle

Saskia Gressel

Nicole Groenke

Mirjam Groh

Anja Guhra

Stephanie Haase

Ulrike Hagen

Anne Hahmann

Tobias Hahn, MSc

Mohamed Haji, MSc

Lilli Hammermüller

Anna Happe-Kramer

Renate Hasenbank

Regine Hasenkopf

Antje Haug

Denise Heidler

Michael Henriksen

Markus Hensel, BTA

Martin Herbst, PhD

Christin Hesse

Sheila Hoffmann

Sabine Horn

Inna Hoyer

Ulrike Hübner

Melanie Humpenöder

Ismail Ishola, PhD

Manuela Jacob

Philipp Jäger, PhD

Marina Jahns

Isabelle Jansen

Sha Jin, PhD

Carmen Judis

Ronny Kalis

Sedef Karayel

Stefanie Kasper

Tina Kausel

Irem Kaymak, Trainee

Birgit Kersten, PhD

Christopher Kessler

Daria Kiesel

Sylvia Kietzmann

Loni Klaus

Daniela Kleckers

Konrad Klockmeier, MSc

Maria Knoblich

Young-In Ko, PhD

Matthias Könn, PhD

Susanne Köppen

Marja Kornhuber

Susanne Kostka

Manuel Krispin

Jeffrey Kroetsch, PhD

Sabrina Kruse

Christin Kuschke

Evangelos Kyriazidis, Trainee

Maciej Lalowski, PhD

Hans Lehrach jr.

Iva Lelios

Megan Leong

Anna Lewandowski

Rahel Lewin

Elena Lucas

Barbara Lucke

Marie Lütke-Eversloh

Melanie Manzke

Phoebe Markovic, PhD

Stefan Maul

Sonia Mazzitelli

Benjamin McMahon

Sascha Mintzlaff

Angeli Möller, PhD

Annekathrin Möller, PhD

Katja Mühlenberg, PhD

Eva-Christina Müller, PhD

Stanley Myers O’Mulloy

Sandra Neuendorf

Cecilia Nicoletti

Hannah Niederlechner, MSc

Julia Niepelt

Anna Norton

Yetunde Odunsi

Leon Olivier

Albrecht Otto, PhD

Inken Padberg

Mary Paniscus, MSc

Christine Petersen, PhD

Spyros Petrakis, PhD

Vanessa Pfiffer

Maria Lucia Pigazzini

Erika Pisch

Stephanie Plassmann, PhD

Pablo Porras Millan, PhD

Anita Pras

Ellen Ramminger, PhD

Tamas Rasko, PhD

Kirstin Rau

Susanne Rautenberg

Alexandra Redel

Sean-Patrick Riechers, PhD

Uli Rockenbauch

Susanne Rohn

Eugenia Rojas

Maxi Rothbart

Dana Rotte

Jenny Russ, PhD

Natalja Rutz

Linda Salzwedel

Maria Saßning

Kati Scharf

Franziska Schiele

Franziska Schindler, PhD

Philipp Schleumann

Sebastian Schmid

Michael Schmidt, PhD

Vera Schmiedel

Stefanie Schneider

Anke Schönherr

Eileen Schormann

Nadja Schräpel

Herwig Schüler, PhD

Margitta Schümann

Paul Schultze-Motel, PhD

Aline Schulz, PhD

Sabrina Schulz

Erik Schweitzer, PhD

Derya Sen

Leticia Serra

Maliha Shah, PhD

Luke Southan

Silke Spading

Selma Staege

Uli Stelzl, PhD

Kerstin Stemmer

Kathrin Stilz

Nadine Strempel, PhD

Sarah Stricker, MD

Martin Strödicke, PhD

Jaana Suopanki-Lalowski, PhD

Bernhard Suter, PhD

Babila Tachu, PhD

Anne Tempelmeier

Pallavi Thaore

Lasse Thiem

Anke Thieme

Jan Timm

Engin Toksoez

Philipp Trepte, PhD

Sofie Trummer

Julia Ucar

Patrick Umbach, PhD

Jose Miguel Urquiza

Tobias Vöpel, PhD

Stephanie Wälter, PhD

Anne Wagner, PhD

Lia Walcher

Jacqueline Walter

Katja Welsch, PhD

Ina Wendland, undergraduate student

Carsta Werner

Franziska Wiedemann

Thomas Wiglenda, PhD

Lindsay Willmore

Sascha Wiswedel

Heike Wobst

Uwe Worm

Sargon Yigit

Oleksandr Zabiegalov

Joshua Zelwis

Jana Zielinski

 

Research

My group's research focusses on ‘Neuroproteomics’, the protein-based investigation of neurodegenerative diseases. In detailed, hypothesis-driven studies we address mechanisms of protein misfolding and aggregation, with the aim of understanding the molecular mechanisms of neurodegeneration in Huntington’s, Alzheimer’s and further diseases causally related to the misfolding of proteins. Our second field of activity is systems biology, in particular using interactomics approaches, which are also mainly applied to neurodegenerative disease processes.

Jan 26, 2021: PhD recruitment round for spring 2021: We are participating. Please check out our lab's project:

How do proteins that interact with mutated huntingtin affect its abundance? A study of Huntington’s disease in cell models and neurons of Drosophila melanogaster

Looking forward to meeting enthusiastic candidates!

 

My group's research focusses on ‘Neuroproteomics’, the protein-based investigation of neurodegenerative diseases. In detailed, hypothesis-driven studies we address mechanisms of protein misfolding and aggregation, with the aim of understanding the molecular mechanisms of neurodegeneration in Huntington’s, Alzheimer’s and further diseases causally related to the misfolding of proteins. In particular, we aim to elucidate the molecular principles by which abnormally folded proteins, their complexes and aggregates cause cellular toxicity and neuronal dysfunction. In our efforts to promote translation of basic research into benefits for patients, we identify and characterize modulators of protein misfolding cascades in disease (Ehrnhoefer et al., Nat Struct Mol Biol, 2008; Bieschke et al., Nat Chem Biol, 2011). We have previously demonstrated that expanded polyglutamine (polyQ) sequences trigger misfolding and aggregation of N-terminal huntingtin fragments in vitro and in vivo (Scherzinger et al., Cell, 1997; Davis et al., Cell, 1997). More recently, we have started new lines of translational research establishing methods to detect disease-relevant misfolded protein species in biosamples from models and patients. These investigations are directed at the development of predictive disease markers which are a prerequisite for the clinical investigation of new disease-modifying therapies targeting neurodegeneration before symptoms of irreversible neuronal damage arise. In collaboration with Alessandro Prigione, a Delbrück Fellow I have been mentoring since 2013, we have established stem cell research strategies for the rare neurological Leigh syndrome and Huntington’s disease (Lorenz et al. Cell Stem Cell, 2017).

Our second field of activity is systems biology, in particular using interactomics approaches, which are also mainly applied to neurodegenerative disease processes. Previously, we developed an automated yeast two-hybrid (Y2H) system, which we used to generate a focused protein-protein interaction network for the huntingtin protein relevant to Huntington's disease (Goehler et al., Mol. Cell, 2004), as well as a large interaction map of the human proteome (Stelzl et al., Cell, 2005). Recently, we identified highly relevant interactions between the triple A ATPase VCP/p97 and an adaptor protein that effects a fundamental structural change in VCP from a homohexamer to a heterooligomer with far-reaching functional implications (Arumughan et al. 2016). We are constantly developing more powerful methods for the identification and validation of protein-protein interactions, most recently LuTHy, a double readout luminescence-based technology for interactome mapping in mammalian cells (Trepte et al., Mol Syst Biol, 2018).

Publications

News

Prof. Dr. Erich Wanker
Prof. Dr. Erich E. Wanker
Group Leader
Contact
Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Robert-Rössle-Str. 10
13125 Berlin, Germany