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Schwarz lab - Institute for Biochemistry

SYNAPTIC TARGETING, CLUSTERING AND RELOCALZATION OF GEPHYRIN BY PHOSPHORYLATION, THIOL-MODIFICATION AND CIS-TRANS ISOMERIZATION

Our project investigates the molecular mechanisms controlling the formation, stabilization and dissociation of inhibitory synapses in the central nervous system of vertebrates. The key molecule of inhibitory synapses is gephyrin, a multi-functional and multi-domain scaffolding protein that binds glycine and GABA type A receptors. Gephyrin is targeted by various types of post-translational modifications, that determine the functional state of the protein. The aim of this project is to dissect the functional role phosphorylation, S-palmitoylation and S-nitrosylation on gephyrin oligomerization, receptor clustering and membrane interaction.

Lukas Flohr

PhD Student since 01.07.2023

EMail: lflohr[at]smail.uni-koeln.de

“I pursued my Bachelor's degree in Biology at the University of Cologne, focusing on mitochondrial import for my thesis. Transitioning to Biochemistry for my Master's, I delved into researching the Molybdenum cofactor and its synthesis enzymes, as well as a disease called MoCD, which arise from defects in cofactor synthesis, under the guidance of Prof. Schwarz. This exploration and research for the mechanism, the localization of enzymes, and the treatment of MoCD continued into my doctoral studies under the same mentorship.”

Theresa Gehling

PhD student since April 2020

EMail: mschne48[at]smail.uni-koeln.de

“I studied biochemistry in cologne and liked this city so much that I stayed for my PhD. It was always my goal to help people, so I'm super happy to do fundamental research in the neuroscience field including real patient cases.”

Nele Burdina

PhD student since January 2020

EMail: nburdina[at]smail.uni-koeln.de

"During my bachelor´s studies in chemistry and my master´s studies in biochemistry I got interested in the fields of structural biology and neurobiochemistry. Thus, I decided to join the lab of Prof. Günter Schwarz for my PhD project to focus on the structural basis of receptor clustering at the inhibitory postsynapse by using single-particle cryo-EM."

Publications

  • AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5. Salscheider SL, Gerlich S, Cabrera-Orefice A, Peker E, Rothemann RA, Murschall LM, Finger Y, Szczepanowska K, Ahmadi ZA, Guerrero-Castillo S, Erdogan A, Becker M, Ali M, Habich M, Petrungaro C, Burdina N, Schwarz G, Klußmann M, Neundorf I, Stroud DA, Ryan MT, Trifunovic A, Brandt U, Riemer J. EMBO J. 2022 Jul 20:e110784. doi: 10.15252/embj.2022110784. Online ahead of print. PMID: 35859387

  • Improving Membrane Activity and Cargo Delivery Efficacy of a Cell-Penetrating Peptide by Loading with Carboranes. Lützenburg T, Burdina N, Scholz MS, Neundorf I. Pharmaceutics. 2021 Dec 3;13(12):2075. doi: 10.3390/pharmaceutics13122075. PMID: 34959356

Selected Publications Schwarz lab

  • Grunewald, N., A. Jan, C. Salvatico, V. Kress, M. Renner, A. Triller, C.G. Specht, and G. Schwarz (2018), Sequences Flanking the Gephyrin-Binding Site of GlyRbeta Tune Receptor Stabilization at Synapses. eNeuro. 5(1).

  • Kumar, A., B. Dejanovic, F. Hetsch, M. Semtner, D. Fusca, S. Arjune, J.A. SantamariaAraujo, A. Winkelmann, S. Ayton, A.I. Bush, P. Kloppenburg, J.C. Meier, G. Schwarz, and A.A. Belaidi (2017), S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. J Clinical Investigation. 127(12): p. 4365-4378.

  • Dejanovic, B., T. Djemie, N. Grunewald, A. Suls, V. Kress, F. Hetsch, D. Craiu, M. Zemel, P. Gormley, D. Lal, E.D.w.g. Euro, C.T. Myers, H.C. Mefford, A. Palotie, I. Helbig, J.C. Meier, P. De Jonghe, S. Weckhuysen, and G. Schwarz (2015), Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy. EMBO Mol Med. 7(12): p. 1580-94.