Structural Neurobiology, Interactions, and Protein Engineering of Receptors (SNIPER)

Welcome to Team SNIPER.

At Team SNIPER, we explore the frontiers of structural neurobiology to uncover how neuronal signaling works in both health and disease. Our research sits at the crossroads of protein engineering, protein design, molecular neuroscience, and structural biology, with a strong focus on synaptic receptor complexes central to brain function and dysfunction.

We employ an integrated toolkit—including mammalian protein expression, biochemical and biophysical analysis, X-ray crystallography, and cryo-electron microscopy—to investigate the molecular architecture and interaction principles of synaptic proteins implicated in neurodevelopmental and neuropsychiatric disorders.

Through antibody and nanobody discovery, as well as protein engineering and design, we create tailored molecular tools to probe, stabilize, and modulate synaptic receptor complexes. These tools support high-resolution structural studies and enable new strategies for therapeutic targeting.

Techniques

  1. Mammalian protein expression
  2. Protein purification and characterization
  3. X-ray crystallography
  4. Cryo-electron microscopy
  5. Biophysical interaction assays
  6. Yeast display
  7. Computational protein design
  8. Site-directed mutagenesis and molecular cloning

Keywords

  • Structural neurobiology
  • Synaptic receptors
  • Protein engineering
  • Protein design
  • Antibody and nanobody discovery
  • Cryo-electron microscopy
  • X-ray crystallography
  • Molecular neuroscience

Selected publications

GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses
Dévina C. Ung, Nicolas Pietrancosta, Elena Baz Badillo, Brigitt Raux, Daniel Tapken, Andjela Zlatanovic, Adrien Doridant, Ben Pode-Shakked, Annick Raas-Rothschild, Orly Elpeleg, Bassam Abu-Libdeh, Nasrin Hamed, Marie-Amélie Papon, Sylviane Marouillat, Rose-Anne Thépault, Giovanni Stevanin, Jonathan Elegheert, Mathieu Letellier, Michael Hollmann, Bertrand Lambolez, Ludovic Tricoire, Annick Toutain, Régine Hepp, Frédéric Laumonnier
Mol Psychiatry. 2024-02-28
10.1038/s41380-024-02469-w

High-Level Production of Recombinant Eukaryotic Proteins from Mammalian Cells Using Lentivirus.
Ester Behiels, Jonathan Elegheert
Methods in Molecular Biology. 2021-01-01
10.1007/978-1-0716-1406-8_4

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits.
Suzuki K, Elegheert J, Song I, Sasakura H, Senkov O, Matsuda K, Kakegawa W, Clayton AJ, Chang VT, Ferrer-Ferrer M, Miura E, Kaushik R, Ikeno M, Morioka Y, Takeuchi Y, Shimada T, Otsuka S, Stoyanov S, Watanabe M, Takeuchi K, Dityatev A, Aricescu AR, Yuzaki M
Science.
10.1126/science.abb4853

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
Kunimichi Suzuki, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Wataru Kakegawa, Amber J. Clayton, Veronica T. Chang, Maura Ferrer-Ferrer, Eriko Miura, Rahul Kaushik, Masashi Ikeno, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Shintaro Otsuka, Stoyan Stoyanov, Masahiko Watanabe, Kosei Takeuchi, Alexander Dityatev, A. Radu Aricescu, Michisuke Yuzaki
. 2020-02-27
10.1101/2020.02.27.967836

Pumping the brakes: suppression of synapse development by MDGA-neuroligin interactions.
Steven A Connor, Jonathan Elegheert, Yicheng Xie, Ann Marie Craig
Current Opinion in Neurobiology. 2019-08-01
10.1016/j.conb.2019.01.002

Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins
Jonathan Elegheert, Ester Behiels, Benjamin Bishop, Suzanne Scott, Rachel E. Woolley, Samuel C. Griffiths, Eamon F. X. Byrne, Veronica T. Chang, David I. Stuart, E. Yvonne Jones, Christian Siebold, A. Radu Aricescu
Nat Protoc. 2018-11-19
10.1038/s41596-018-0075-9

Calibration-free in vitro quantification of protein homo-oligomerization using commercial instrumentation and free, open source brightness analysis software
Rory Nolan, Luis A. Alvarez, Samuel C. Griffiths, Jonathan Elegheert, Christian Siebold, Sergi Padilla-Parra
JoVE. 2018-07-17
10.3791/58157

Structural dissection of Shewanella oneidensis old yellow enzyme 4 bound to a Meisenheimer complex and (nitro)phenolic ligands
Jonathan Elegheert, Ann Brigé, Jozef Van Beeumen, Savvas N. Savvides
FEBS Lett. 2017-09-15
10.1002/1873-3468.12833

Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins.
Jonathan Elegheert, Vedrana Cvetkovska, Amber J. Clayton, Christina Heroven, Kristel M. Vennekens, Samuel N. Smukowski, Michael C. Regan, Wanyi Jia, Alexandra C. Smith, Hiro Furukawa, Jeffrey N. Savas, Joris de Wit, Jo Begbie, Ann Marie Craig, A. Radu Aricescu
Neuron. 2017-09-01
10.1016/j.neuron.2017.07.040

nandb-number and brightness in R with a novel automatic detrending algorithm.
Rory Nolan, Luis A J Alvarez, Jonathan Elegheert, Maro Iliopoulou, G Maria Jakobsdottir, Marina Rodriguez-Muñoz, A Radu Aricescu, Sergi Padilla-Parra
Bioinformatics. 2017-07-11
10.1093/bioinformatics/btx434

Structural basis for integration of GluD receptors within synaptic organizer complexes.
Jonathan Elegheert, Wataru Kakegawa, Jordan E. Clay, Natalie F. Shanks, Ester Behiels, Keiko Matsuda, Kazuhisa Kohda, Eriko Miura, Maxim Rossmann, Nikolaos Mitakidis, Junko Motohashi, Veronica T. Chang, Christian Siebold, Ingo H. Greger, Terunaga Nakagawa, Michisuke Yuzaki, A. Radu Aricescu
Science. 2016-07-14
10.1126/science.aae0104

Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1.
Jan Felix, Steven De Munck, Kenneth Verstraete, Leander Meuris, Nico Callewaert, Jonathan Elegheert, Savvas N. Savvides
Structure. 2015-09-01
10.1016/j.str.2015.06.019

Structure and functional properties of Norrin mimic Wnt for signalling with Frizzled4, Lrp5/6, and proteoglycan.
Tao-Hsin Chang, Fu-Lien Hsieh, Matthias Zebisch, Karl Harlos, Jonathan Elegheert, E Yvonne Jones
eLife. 2015-07-09
10.7554/eLife.06554

Repulsive guidance molecule is a structural bridge between neogenin and bone morphogenetic protein.
Eleanor G Healey, Benjamin Bishop, Jonathan Elegheert, Christian H Bell, Sergi Padilla-Parra, Christian Siebold
Nat Struct Mol Biol. 2015-05-04
10.1038/nsmb.3016