E. Wanker Lab

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.

April 5, 2019

Junior scientists with a passion for interactomics and neurodegeneration, please apply! 

Job advert is out at:
https://www.nature.com/naturecareers/job?id=684527
https://www.mdc-berlin.de/career/jobs/postdoctoral-researcher-mfd
https://www.jobvector.de/jobs-stellenangebote/biologie-life-sciences/forschung-entwicklung/natural-scientist-postdoctoral-researcher-neuroproteomics-116120.html?suid=9cb2c8217d1314611c52992c0b4a444db86a4091

We are currently starting the search for a postdoc in the INTERACTOMICS of Huntington's disease. We are looking for highly qualified researchers to develop new approaches for the detection of protein-protein and protein-drug interactions in mammalian cells using endogenous proteins – all with a view to delve deep into the network biology of HD. Look out for our job ad that will appear shortly on this website and on naturecareers! If you are interested contact us. To find out more, look at our recent paper: LuTHy: a double‐readout bioluminescence‐based two‐hybrid technology for quantitative mapping of protein–protein interactions in mammalian cells. http://msb.embopress.org/content/14/7/e8071
https://edoc.mdc-berlin.de/17591/

January 2019

Look at our exciting recent study and highly innovative amyloid-beta seeding assay in our recent paper:

Annett Boeddrich, Julius T. Babila, Thomas Wiglenda et al., The Anti-amyloid Compound DO1 Decreases Plaque Pathology and Neuroinflammation-Related Expression Changes in 5xFAD Transgenic Mice. Cell Chemical Biology, 2019 Jan 17;26(1):109-120.e7. doi: 10.1016/j.chembiol.2018.10.013.

September 2018
We would like to proudly announce our recent papers in the areas of protein aggregation in Huntington's disease and of protein-protein interaction mapping:

Anne Ast, Alexander Buntru, Franziska Schindler 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
doi: 10.1016/j.molcel.2018.07.032

Philipp 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.
doi: 10.15252/msb.20178071

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).