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André Nadler

MPI-CBG | Research Group Leader

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  • Basic Research

    Structure of membrane
    Signaling
    Lipid metabolism

  • Technology & Resources

    Technologies

Project Description

The aim of the Nadler lab is to develop new experimental approaches that will ultimately allow us to understand the cellular function of lipids in a more quantitative fashion. Specifically, we develop new chemical probes for modulating cellular lipid levels and lipid visualization. We have established an additional focus on the development of new lipid biosensors for monitoring dynamic changes of lipid levels during cellular processes. Over the last years, we have pioneered the development of organelle specific caged lipids, that allow to trigger acute lipid concentration increases in well-defined cellular compartments (Nadler et al., Nat. Commun., Wagner et al., Angew. Chem. Int. Ed. 2018). This technology constitutes a significant step forward compared to genetic or pharmacological approaches, which typically result in pleiotropic changes in the entire lipidome or affect lipid levels in the entire cell.
We are now at a point where we are able to induce well-defined, acute lipid concentration increases in individual cellular membrane leaflets and use this experimental capacity to build quantitative kinetic models of cellular lipid signalling events. Together with the Walter lab (Leibnitz Institute, Berlin) we succeeded in determining quantitative dissociation constants for lipid-protein interactions in the DAG-PKC signalling cascade and can for the first time analyse the effects of lipid diversity in cellular signalling cascades in live cell experiments.
Together with the Zerial and Honigmann laboratories we are currently implementing a newly developed two-color super-resolution lipid imaging approach based to study lipid transport processes in cell polarity and stress responses.

Fig.: Organelle-targeted caged lipids enable modulation of lipid levels with subcellular specificity

  • Collection of Lipid Center relevant Publications

    2018
    Wagner N, Stephan M, Höglinger D, Nadler A. A Click Cage: Organelle-Specific Uncaging of Lipid Messengers. Angew Chem Int Ed Engl. 2018 Oct 1;57(40):13339-13343

    Honigmann A, Nadler A. The Next Frontier: Quantitative Biochemistry in Living Cells. Biochemistry. 2018 Jan 9;57(1):47-55

    2017
    Walter AM, Müller R, Tawfik B, Wierda KD, Pinheiro PS, Nadler A, McCarthy AW, Ziomkiewicz I, Kruse M, Reither G, Rettig J, Lehmann M, Haucke V, Hille B, Schultz C, Sørensen JB. Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis. Elife. 2017 Oct 25;6

    Zuidscherwoude M, Dunlock VE, van den Bogaart G, van Deventer SJ, van der Schaaf A, van Oostrum J, Goedhart J, In ‘t Hout J, Hämmerling GJ, Tanaka S, Nadler A, Schultz C, Wright MD, Adjobo-Hermans MJW, van Spriel AB. Tetraspanin microdomains control localized protein kinase C signaling in B cells. Sci Signal. 2017 May 9;10(478)

    Höglinger D, Nadler A, Haberkant P, Kirkpatrick J, Schifferer M, Stein F, Hauke S, Porter FD, Schultz C. Trifunctional lipid probes for comprehensive studies of single lipid species in living cells. Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1566-1571

    2016
    Hövelmann F, Kedziora KM, Nadler A, Müller R, Jalink K, Schultz C. Optotaxis: Caged Lysophosphatidic Acid Enables Optical Control of a Chemotactic Gradient. Cell Chem Biol. 2016 May 19;23(5):629-634

    Yushchenko DA, Nadler A, Schultz C. Manipulating cell signaling with subcellular spatial resolution. Cell Cycle. 2016;15(8):1023-4

    Bilgin M, Born P, Fezza F, Heimes M, Mastrangelo N, Wagner N, Schultz C, Maccarrone M, Eaton S, Nadler A, Wilm M, Shevchenko A. Lipid Discovery by Combinatorial Screening and Untargeted LC-MS/MS. Sci Rep. 2016 Jun 17;6:27920

    2015
    Nadler A, Yushchenko DA, Müller R, Stein F, Feng S, Mulle C, Carta M, Schultz C. Exclusive photorelease of signalling lipids at the plasma membrane. Nat Commun. 2015 Dec 21;6:10056