Prof. Christoph Fahlke

Christoph Fahlke is interested in understanding the molecular mechanism and cellular functions of membrane transporters. His group employs a multi scape approach, ranging from computational approaches to describe protein functions at atomic resolution to analyzing animal models to study the pathophysiology of human diseases such as myotonia, episodic ataxia or epilepsy.

After obtaining a Master degree in Physics and finishing medical school in Ulm, Christoph Fahlke joined the Department of General Physiology in Ulm as Postdoc to study the molecular and cellular pathophysiology of Myotonia. He did additional postdoctoral training at Vanderbilt University between 1995 and 1996, where he became Instructor and later Assistant Professor of Pharmacology and Medicine. In 1999 he returned to Germany as Professor of Physiology at RWTH Aachen. After serving as Chairperson of Neurophysiology at the Medizinische Hochschule Hannover between 2005 and 2012, he joined Forschungszentrum Jülich as Director and Division Chief of the Institute of Biological Information Processing 1 and Professor of Biophysics at the Heinrich Heine University Düsseldorf in 1992.

Selected Publications

1. Fahlke Ch, Rüdel R, Mitrovic N, Zhou M, George AL (1995). An aspartic acid important for voltage-dependent gating of human muscle chloride channels. Neuron 15, 463-472. (doi.org/10.1016/0896-6273(95)90050-0)

2. Beck CL, Fahlke Ch, George AL (1996). Molecular basis for decreased muscle chloride conductance in the myotonic goat. Proc Natl Acad Sci USA 93, 11248-11252. (doi.org/10.1073/pnas.93.20.11248)

3. Fahlke Ch, Beck CL, George AL (1997). A mutation in autosomal dominant myotonia congenita affects pore properties in the muscle chloride channel. Proc Natl Acad Sci USA 94, 2729-2734. (doi.org/10.1073/pnas.94.6.2729)

4. Fahlke Ch, Yu HT, Beck CL, Rhodes TH, George AL (1997). Pore-forming segments in voltage-gated Cl^- channels. Nature 390, 529-532. (doi.org/10.1038/37391)

5. Fahlke Ch, Rhodes TH, Desai RR, George AL (1998). Pore stoichiometry of a voltage-gated chloride channel. Nature 394, 687-690. (doi.org/10.1038/29319)

6. Wu FF, RyanA, Devaney J, Korade-MirnicsZ, Warnstedt M, Poser B, PegoraroE, YeeAS, FeliceKJ, GiulianiMJ, MayerRF, PalmucciL, MarinoM, Rüdel R, HoffmanEP, FahlkeCh (2002). Novel CLCN1 mutations with unique clinical and electrophysiological consequences. Brain 125, 2392-2407. (doi.org/10.1093/brain/awf246)

7. Melzer N, Torres-Salazar D, Fahlke Ch (2005). A dynamic switch between inhibitory and excitatory currents in a neuronal glutamate transporter. Proc Natl Acad Sci USA 102, 19215‑1218. (doi.org/10.1073/pnas.0508837103)

8. Scholl U, Hebeisen S, Janssen AGH, Müller-Newen G, Alekov A, Fahlke Ch (2006). Barttin modulates trafficking and function of ClC-K channels. Proc Natl Acad Sci USA 103, 11411-11416. (doi.org/10.1073/pnas.0601631103)

9. Janssen AG, Scholl U, Domeyer C, Nothmann D, Leinenweber A, Fahlke Ch (2009). Disease-causing dysfunctions of barttin in Bartter syndrome type IV. J Am Soc Nephrol 20, 145-153. (doi.org/10.1681/asn.2008010102)

10. Riazuddin S, Anwar S, Fischer M, Ahmed ZM, Khan SY, Janssen AG, Zafar AU, Scholl U, Husnain T, Belyantseva IA, Friedman PL, Riazuddin S, Friedman TB, Fahlke Ch (2009). Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome. Am J Hum Genet 85, 273-280. (doi.org/10.1016/j.ajhg.2009.07.003)

11. Fischer M, Janssen AG, Fahlke Ch (2010). Barttin activates ClC-K channel function by modulating gating. J Am Soc Nephrol 21, 1281-1289. (doi.org/10.1681/asn.2009121274)

12. Neuwelt EA, Bauer B, Fahlke Ch, Fricker G, Iadecola C, Janigro D, Leybaert L, Molnar Z, O'Donnell ME, Povlishock JT, Saunders NR, Sharp F, Stanimirovic D, Watts RJ, Drewes LR (2011). Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci 12:169-182. (doi.org/10.1038/nrn2995)

13. Winter N, Kovermann P, Fahlke Ch (2012). A point mutation associated with episodic ataxia 6 increases glutamate transporter anion currents. Brain 135, 3416-3425 (doi: 10.1093/brain/aws255)

14. Scholl UI, Goh G, Stölting G, Campos de Oliveira R, Choi M, Overton JD, Fonseca AL, Korah R, Starker LF, Kunstman JW, Prasad M, Hartung EA, Mauras E, Benson MR, Brady T, Shapiro JR, Loring E, Nelson-Williams C, Libutti SK, Mane S, Hellman P, Westin G, Åkerström G, Björklund P, Carling T, Fahlke Ch, Hidalgo P, Lifton RP (2013). Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat Genet 45,1050-1054 (doi: 10.1038/ng.2695)

15. Ewers D, Becher T, Machtens JP, Weyand I, Fahlke Ch (2013). Induced-fit substrate binding to an archeal glutamate transporter homologue. Proc Natl Acad Sci USA 110, 12486-12491 (doi: 10.1073/pnas.1300772110)

16. Machtens JP, Kortzak D, Lansche C, Leinenweber A, Kilian P, Begemann B, Zachariae U, Ewers D, de Groot B, Briones R, Fahlke Ch (2015) Mechanisms of anion conduction by coupled glutamate transporters. Cell 160, 542-53 (doi: 10.1016/j.cell.2014.12.035)

17. Gushchin I, Shevchenko V, Polovinkin V, Kovalev K, Alekseev A, Round E, Borshchevskiy V, Balandin T, Popov A, Gensch T, Fahlke Ch, Bamann C, Willbold D, Büldt G, Bamberg E, Gordeliy V (2015) Crystal structure of a light-driven sodium pump. Nat Struct Mol Biol 22,390-395 (doi:10.1038/nsmb.3002)

18. Martineau M, Guzman RE, Fahlke Ch, Klingauf J (2017). VGLUT1 functions as a glutamate/proton exchanger with a chloride channel activity at hippocampal glutamatergic terminals. Nat Comm 8, 2279 (doi:10.1038/s41467-017-02367-6)

19. Scholl UI, Stölting G, Schewe J, Thiel A, Tan H, Nelson-Williams C, Vichot AA, Jin SC, Loring E, Untiet V, Yoo T, Choi J, Xu S, Wu A, Kirchner M, Mertins P, Rump LC, Onder AM, Gamble C, McKenney D, Lash RW, Jones DP, Chune G, Gagliardi P, Choi M, Gordon R, Stowasser M, Fahlke Ch, Lifton RP (2018). CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet 50, 349-354(doi: 10.1038/s41588-018-0048-5)

20. Kortzak D, Alleva C, Weyand I, Ewers D, Zimmermann MI, Franzen A, Machtens JP, Fahlke Ch (2019). Allosteric gate modulation confers K⁺ coupling in glutamate transporters. Embo J 38, e101468 (doi: 10.15252/embj.2019101468).

21. Bratanov D, Kovalev K, Machtens JP, Astashkin R, Chizhov I, Soloviov D, Volkov D, Polovinkin V, Zabelskii D, Mager T, Gushchin I, Rokitskaya T, Antonenko Y, Alekseev A, Shevchenko V, Yutin N, Rosselli R, Baeken C, Borshchevskiy V, Bourenkov G, Popov A, Balandin T, Büldt G, Manstein D, Rodriguez-Valera F, Fahlke Ch, Bamberg E, Koonin E, Gordeliy V (2019). Unique structure and function of viral rhodopsins. Nat Comm 10, 4939(doi.org/10.1038/s41467-019-12718-0)

22. Schewe J, Seidel E, Forslund S, Markó L, Peters J, Müller D, Fahlke Ch, Stölting G, Scholl UI (2019). Elevated aldosterone and blood pressure in a mouse model of familial hyperaldosteronism with ClC-2 mutation. Nat Comm 10, 5155 (doi: 10.1038/s41467-019-13033-4)

23. Grieschat M, Guzman RE, Langschwager K, Fahlke Ch, Alekov AK (2020). Metabolic energy sensing by mammalian CLC anion/proton exchangers. Embo Rep 21, e47872 (doi: 10.15252/embr.201947872)

24. Kovermann P, Untiet V, Kolobkova Y, Engels M, Baader S, Schilling K, Fahlke Ch (2020). Increased glutamate transporter-associated anion currents cause glial apoptosis in episodic ataxia 6. Brain Comms fcaa022 (doi.org/10.1093/braincomms/fcaa022)

25. Chiariello MG, Bolnykh V, Ippoliti E, Meloni S, Olsen JMH, Beck T, Rothlisberger U, Fahlke Ch, Carloni P (2020). Molecular basis of CLC antiporter inhibition by fluoride. J Am Chem Soc 142, 7254-7258 (doi:10.1021/jacs.9b13588)

26. Alleva C, Kovalev K, Astashkin R, Berndt MI. Baeken C, Balandin T, Gordeliy V, Fahlke Ch, Machtens JP (2020). Na⁺-dependent gate dynamics and electrostatic attraction ensure substrate coupling in glutamate transporters. Sci Adv 6, eaba9854 (doi: 10.1126/sciadv.aba9854)

27. Fahlke Ch, Linke W, Raßler B, Wiessner R (2022). Taschenatlas Physiologie mit Grundlagen der Pathophysiologie (3. Auflage), Elsevier.

28. Tan HL, Bungert-Plümke S, Kortzak D, Fahlke Ch, Stölting G (2022). Determination of protein stoichiometries via dual-color colocalization with single molecule localization microscopy. Elife 11, e76631 (doi: 10.7554/eLife.76631)

29. Kolen B, Borghans B, Kortzak D, Lugo V, Hannack C, Guzman R, Ullah G, Fahlke Ch (2023). Vesicular glutamate transporters are H⁺-anion exchangers that operate at variable stoichiometry.Nat Comm 14, 2723 (doi: 10.1038/s41467-023-38340-9)

30. Dmitrieva N, Gholami S, Alleva C, Carloni P, Alfonso-Prieto M, Fahlke Ch. Transport mechanism of DgoT, a bacterial homolog of SLC17 organic anion transporters. EMBO J 43, 6740 – 6765 (doi.org/10.1038/s44318-024-00279-y)