Scholz Lab

The main goal of our work is to gain a mechanistic understanding of how cell and tissue mechanics are controlled and how these mechanisms intersect with developmental, metabolic and functional aspects of nervous tissues under physiological and pathophysiological conditions. To this end, we are investigating mechano-neurobiological questions at different scales.

​Adhesion GPCR and other membrane proteins

We are interested in understanding the biology of molecular force sensors that are relevant for establishing and maintaining the mechanical profile of neural cell types. Adhesion GPCR are with their mechanosensitive capacities are currently at the center of this scientific endeavor and we aim to solve some of the mysteries surrounding these large cell surface proteins, including:​

• the underpinnings of adhesion GPCR activation and signaling
• the biological rationale for the vivid splicing activities of adhesion GPCR
• their ligand profile and whether adhesion GPCR are part of macromolecular protein complexes and/or functional units e.g. with other mechanosensors
• how malfunction of adhesion GPCR contributes to disease initiation and progression (e.g. glaucoma and cancer) 

Aside from adhesion GPCR we are studying Integrins, Polycystines, Toll-like receptors and Piezo proteins. ​

Cell and Tissue Mechanics

In a process referred to as 'mechanical tension homeostasis' neurons can actively modulate their tension profile i.e. axons seem to have the capacity to adapt and maintain their mechanical tension profile in a changing mechanical microenvironment. Arising from this phenomenon, we are interested in understanding:

• the molecular mechanisms that underlie mechanical tension homeostasis and especially the identity of the mechanosensing cell surface protein(s)
• if and how mechanical tension adaptation relates to adequate form and function of synapses
• if and how mechanical tension adaptation interconnects with metabolic facets and age-related changes
• how mechanical tension adaptation impacts animal behavior

The Aging Brain

In a collaborative effort with the Vardjan lab (University of Ljubljana), we are aiming to dissect how intracellular signaling and metabolite content of the brain changes with age and how this affects brain morphology, function and behavioral traits e.g. movement.

New directions

• Cellular mechanics in neuro-oncology
• Molecular mechanisms of sleep-dependent brain detox

• Investigation of cell and tissue mechanics  
  (previously funded through a Junior grant from the Medical Faculty, Leipzig University; development of TSMod-based force sensors in cooperation with Prof. M. Krieg, ICFO, Barcelona)​

• Functional analysis of the adhesion GPCR class in Drosophila
  (previously DFG-funded within FOR2149; Cooperation with Prof. T. Langenhan, Leipzig University, Germany)

• Dynamic modulation of adhesion GPCR function through complex formation
  (DFG-funded within CRC1423; Cooperation with Prof. T. Langenhan, Leipzig University, Germany)

• Molecular dynamics of adhesion GPCR
  (Cooperation with Prof. P. Hildebrand, Leipzig University, Germany)

• Structure Function of aGPCR-ligand pairs
  (Cooperation with Prof. N. Sträter, Leipzig University, Germany)

• Understanding mechanosensitivity of sensory neurons
  (Cooperation with Dr. D. Ljaschenko, Leipzig University, Germany)

• G protein biology and downstream signaling of adhesion GPCR
  (Cooperation with Prof. E. Kostenis, University of Bonn, Germany)

• Adhesion GPCR function in Drosophila locomotion
  (Cooperation with Prof. M. Schleyer, Hokkaido University, Japan)

• Adhesion GPCR function in optical system of Drosophila
  (Cooperation with Ko-Fan Chen, University of Leicester, England)

• Pharmacological Search method for adhesion GPCR compounds
  (Cooperation with Prof. T. Langenhan, Leipzig University, Germany)

• Modulation of adhesion GPCR function to treat Glaucoma
  (Cooperation with Prof. C. O'Brien, Mater Misericordiae University Hospital, Dublin, Ireland)

• Investigation of metabolic changes in the aging Drosophila brain
  (previously DAAD-funded, P33; Cooperation with Prof. N. Vardjan, University of Ljubljana, Slovenia)

​

• ​Anne Bormann - (PhD Candidate)
• Lara-Sophie Brodmerkel​ - (MD Candidate; jointly with Ljaschenko lab)
• Max Buhlan - (MD candidate; jointly with Langenhan lab)
• Lucia Ernst​ - (MD Candidate)
• Marie-Sophie Gläser - (MD Candidate; jointly with Ljaschenko lab)
• Marguerite Kemkemer - (MD Candidate; jointly with Langenhan lab)
• Marek B. Körner (M.Sc. Student; jointly with Mrestani lab)
• Michal Mitro​ (PhD Candidate)​
• Hauke Staake - (MD Candidate)
• Clemens Szykownik - (Student helper)
• Collaboration with Mrestani group (Clinician Scientist)
• Collaboration with Langenhan group
• Collaboration with Ljaschenko group​​​

BMBF - VIP+ Project Team (jointly with T. Langenhan)

• ​Anne-Kristin Dahse - (PhD Candidate)
  
• ​Berkay Demirbas - (PhD Candidate)
• ​Stephanie Häfner - (PostDoc)
• Svenja Kapplinghaus - (Technical Assistance)
• Christoph-Otto Naumann - (Technical Assistance)
• Prabakaran A.​ - (PhD Candidate)

Former members

• Carlo Eberlein (B.Sc. Student 2020; jointly with Langenhan lab)
• Johanna Irmer (M.Sc. Student 2018; jointly with Langenhan lab)
• Joris Lehmann (M.Sc. Student 2020; jointly with Ljaschenko lab)
• Anna-Luka Ober (M.Sc. Student 2020)

Original Research –​ peer reviewed 

(*Equal contribution /​ ^#Correspondence & Last Author / ¹Maiden name)

Vieira Contreras F^*, Auger GM^*, Müller L, Richter V, Huetteroth W, Seufert F, Hildebrand PW, Scholz N, Thum AS, Ljaschenko D, Blanco-Redondo B, Langenhan T (2024). The adhesion G-protein-coupled receptor mayo/CG11318 controls midgut development in Drosophila. Cell Rep, 43, 113640. Doi: 10.1016/j.celrep.2023.113640

Buhlan M, Ljaschenko D, Scholz N^#, Langenhan T^# (2024). Experimental modulation of physiological force application on leg joint neurons in intact Drosophila melanogaster. Nat Protoc, 19, 113-126.

Fei Lin, Ruijing Tang, Chong Zhang, Nicole Scholz, Georg Nagel, Shiqiang Gao^#​ (2023). Combining differenz ion-selective channelrhodopsins to control water flux by light. Pflug Arch - Eur J Physiolol. Doi: 10.1007/00424-023-02853-5.

Michael Thane, Emmanouil Paisios, Torsten Ströter, Anna-Rosa Krüger, Sebastian Gläß, Anne-Kristin Dahse, Nicole Scholz, Bertram Gerber, Dirk J. Lehmann, Michael Schleyer^#. High-resolution analysis of individual Drosophila melanogaster larvae within groups uncovers inter- and intra-individual variability in locomotion and its neurogenetic modulation. Open Biol. 13(4):220308. Doi: 10.1098/rsob.220308.

Nicole Scholz^*,#, Anne-Kristin Dahse^*, Marguerite Kemkemer, Anne Bormann, Genevieve M. Auger, Fernando Vieira Contreras, Lucia F. Ernst, Hauke Staake, Marek B. Körner, Amelie Meyer-Mölck, Yin-Kwan Chung, Beatriz Blanco-Redondo, Franziska Klose, Mohamed Ali Jarboui, Dmitrij Ljaschenko, Tobias Langenhan^# (2023). Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation. Nature. 615(7954); 945-953. Doi: 10.1038/s41586-023-05802-5.

Marek B. Körner^*, Akhil Velluva^*, Linnaeus Bundalian, Maximilian Radtke, Chen-Ching Lin, Pia Zacher, Tobias Bartolomaeus, Anna S. Kirstein, Achmed Mrestani, Nicole Scholz, Konrad Platzer, Anne-Christin Teichmann, Julia Hentschel, Tobias Langenhan, Johannes R. Lemke, Antje Garten, Rami Abou Jamra^#, Diana Le Duc^# (2022). Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion. Scientific Reports, 12(1)13507. Doi:10.1038/s41598-022-17604-2.

Katharina J Götze, Achmed Mrestani, Paula Beckmann, Knut Krohn, Diana Le Duc, Akhil Velluva, Mathias A Böhme, Manfred Heckmann, Rami Abou Jamra, Johannes R Lemke, Hendrik Bläker, Nicole Scholz, Dmitrij Ljaschenko^#, Tobias Langenhan^# (2022). Improving one-step scarless genome editing in Drosophila melanogaster by combining ovo^D co-CRISPR selection with sgRNA target site masking.  Biology Methods and Protocols. 7(1): bpac003. Doi: 10.1093/biomethods/bpac003.

Mila M Paul^*, Sven Dannhäuser^*, Lydia Morris^*, Achmed Mrestani^*, Martha Hübsch, Jennifer Gehring, Georgios N Hatzopoulos, Martin Pauli, Genevieve M Auger, Grit Bornschein, Nicole Scholz, Dmitrij Ljaschenko, Martin Müller, Markus Sauer, Hartmut Schmidt, Robert J Kittel, Aaron DiAntonio, Ioannis Vakonakis, Manfred Heckmann^#, Tobias Langenhan^# (2022). The human cognition-enhancing CORD7 mutation increases active zone number and synaptic release. Brain. awac011, Doi:10.1093/brain/awac011.

Ulli Heydasch, Renate Kessler, Jan-Peter Warnke, Klaus Eschrich, Nicole Scholz^#, Marina Bigl^# (2021). Functional diversity of PFKFB3 splice variants in glioblastoma. PloS One. 16(7): e0241092. Doi: 10.1371/journal.pone.0241092.

Tina Smolič, Petra Tavčar, Anemari Horvat, Urška Černe, Ana Halužan Vasle, Larisa Tratnjek, Mateja Erdani Kreft, Nicole Scholz, Maja Matis, Toni Petan, Robert Zorec, Nina Vardjan^# (2021). Astrocytes in stress accumulate lipid droplets. Glia. 69(6):1540-1562. Doi: 10.1002/glia.23978.

Gerti Beliu^*, Steffen Altrichter^*, Ramon Guixà-González^*, Mareike Hemberger, Ina Brauer, Anne-Kristin Dahse, Nicole Scholz, Robert Wieduwild, Alexander Kuhlemann, Hossein Batebi, Florian Seufert, Pérez-Hernández G, Peter W. Hildebrand^#, Markus Sauer^#, Tobias Langenhan^# (2021).  Tethered agonist exposure in intact adhesion/class B2 GPCRs through intrinsic structural flexibility of the GAIN domain. Mol Cell. Doi: 10.1016/j.molcel.2020.12.042.

Beatriz Blanco-Redondo^#, Nidhi Nuwal, Susanne Kneitz, Tulip Nuwal, Partho Halder, Yiting Liu, Nadine Ehmann, Nicole Scholz, Annika Mayer, Jörg Kleber, Thilo Kähne, Dominique Schmitt, Madhumala K. Sadanandappa, Natalja Funk, Viera Albertova, Charlotte Helfrich-Förster, Mani Ramaswami, Gaiti Hasan, Robert J. Kittel, Tobias Langenhan, Bertram Gerber, and Erich Buchner^# (2019). Implications of the Sap47 null mutation for synapsin phosphorylation, longevity, climbing, and behavioural plasticity in adult Drosophila. J Exp Biol. Doi: 10.1242/jeb.203505.

Nicole Scholz, Tobias Langenhan^#, Torsten Schöneberg^# (2019). Revisiting the classification of adhesion GPCRs. Ann NY Acad Sci. 1456(1):80-95. Doi: 10.1111/nyas.14192.

Nicole Scholz^*, Nadine Ehmann^*, Divya Sachidanandan, Cordelia Imig, Benjamin H. Cooper, Olaf Jahn, Kerstin Reim, Nils Brose, Jutta Meyer, Marius Lamberty, Steffen Altrichter, Anne Bormann, Stefan Hallermann, Martin Pauli, Manfred Heckmann, Christian Stigloher, Tobias Langenhan^#, Robert J. Kittel^# (2018). Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix. J Cell Biol. 218(3): 1011–1026. Doi: 101083/jcb.201806155.

Nicole Scholz^*, Chonglin Guan^*, Matthias Nieberler^*, Alexander Grotemeyer^*, Isabella Maiellaro, Shiqiang Gao, Sebastian Beck, Matthias Pawlak, Markus Sauer, Esther Asan, Sven Rothemund, Jana Winkler, Simone Prömel, Georg Nagel, Tobias Langenhan^#, Robert J. Kittel^# (2017). Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons. eLife 6: e28360. Doi: 10.7554/eLife.28360.

Related Insight article by Wayne A Johnson. Mechanotransduction: Two views of the same stimulus.

Nicole Scholz^*, Jennifer Gehring^*, Chonglin Guan^*, Dmitrij Ljaschenko, Robin Fischer, Vetrivel Lakshmanan, Robert J. Kittel^#, Tobias Langenhan^# (2015). The Adhesion-GPCR Latrophilin/CIRL shapes mechanosensation. Cell Rep. 11(6): 866-874. Doi: 10.1016/j.celrep.2015.04.008.

Original Research – non-peer-reviewed

Anne Bormann^*, Marek B. Körner^*, Anne-Kristin Dahse^*, Marie S. Gläser, Johanna Irmer, Vera Lede, Judith Alenfelder, Joris Lehmann, Daniella C.N. Hall, Michael Thane, Michael Schleyer, Eva Kostenis, Torsten Schöneberg, Marina Bigl, Tobias Langenhan, Dmitrij Ljaschenko^#, Nicole Scholz^#​ (2023). Intron retention of an adhesion GPCR generates single transmembrane-helix isoforms to enable 7TM-adhesion GPCR function. Biorxiv. Doi: 10.1101/2023.01.11.521585.

Reviews

Birgül Iyison N^*,#, Abboud C, Abboud D, Abdulrahman AO, Bondar AN, Dam J, Georgoussi Z, Giraldo J, Horvat A, Karoussiotis C, Paz-Castro A, Scarpa M, Schihada H, Scholz N, Güvenc Tuna B, Vardjan N^*,# (2024). Physiology of GPCRs in the Nervous System and the contribution of Orphan GPCRs. Br J Pharmacol. Jun 2. doi: 10.1111/bph.16389. Online ahead of print.PMID: 38825750 Review. ​

Ines Liebscher^#, Orkun Cevheroğlu, Cheng-Chih Hsiao, André F Maia, Hannes Schihada, Nicole Scholz, Mark Soave, Katja Spiess, Katarina Trajković, Mickey Kosloff, Simone Prömel^# (2021). A Guide to Adhesion GPCR research. FEBS journal. 289(24):7610-7630.  Doi: 10.1111/febs.16258.

Morgan RK, Anderson GR, Araç D, Aust G, Balenga N, Boucard A, Bridges JP, Engel FB, Formstone CJ, Glitsch MD, Gray RS, Hall RA, Hsiao CC, Kim HY, Knierim AB, Kusuluri DK, Leon K, Liebscher I, Piao X, Prömel S, Scholz N, Srivastava S,Thor D, Tolias KF, Ushkaryov YA, Vallon M, Van Meir EG, Vanhollebeke B, Wolfrum U, Wright KM, Monk KR, Mogha A^# (2019). The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors. Ann NY Acad Sci. 1456(1):5-25. Doi:10.1111/nyas.14094.

Nicole Scholz^# (2018). Cancer Cell Mechanics: Adhesion G Protein-Coupled Receptors in Action? Front. Oncol. 8:59. Doi.org/10.3389/fronc.2018.00059.

Ines Liebscher, Brian Ackley, Demet Araç, Donna M. Ariestanti, Gabriela Aust, Byoung-il Bae, Bigyan R. Bista, James P. Bridges, Joseph G. Duman, Felix B. Engel, Stefanie Giera, Andre' M. Goffinet, Randy A. Hall, Jörg Hamann, Nicole Hartmann¹, Hsi-Hsien Lin, Mingyao Liu, Rong Luo, Amit Mogha, Kelly R. Monk, Miriam C. Peeters, Simone Prömel, Susanne Ressl, Helgi B. Schiöth, Severine M. Sigoillot, Helen Song, William S. Talbot, Gregory G. Tall, James P. White, Uwe Wolfrum, Lei Xu, and Xianhua Piao^# (2014). New functions and signaling mechanisms for the class of adhesion G protein–coupled receptors. Ann NY Acad Sci, 1333(1): 43-64. Doi: 10.1111/nyas.12580.

Book Chapters

Nicole Scholz^#, Kelly Monk, Robert J. Kittel, Tobias Langenhan^# (2016). Adhesion GPCRs as a putative Class of Metabotropic Mechanosensors. In: Langenhan T, Schöneberg T (eds) Adhesion G protein-coupled receptors: molecular, physiological and pharmacological principles in health and disease. Handb Exp Pharmacol, Springer, Heidelberg; 234:221-247. Doi: 10.1007/978-3-319-41523-9_10.

Patents pending or issued

Langenhan T, Scholz N (2020). Chimeric sensor protein and methods of use thereof. Priority application: EP 3974535. WO/2022/063915 (pending).​