Retourner en haut

Structural Biology and Engineering of Neuronal Proteins

Team Leader : Jonathan Elegheert

Jonathan Elegheert joined the IINS in 2019 as a team leader, sponsored by an Initiative of Excellence (IdEx) Junior Chair (University of Bordeaux) and a Neurocampus starting package (Regional Council of Nouvelle Aquitaine). In 2019, he was recruited to the CNRS, was a laureate of the CNRS-Inserm ATIP-Avenir program and obtained an ERC Starting Grant.

After studying medicine (BSc) and biochemistry (MSc), he obtained his PhD in 2012 from Ghent University (Belgium), where he studied the structural biology of Colony-Stimulating Factor 1 (CSF-1) cytokine signalling in the lab of Prof. Savvas N. Savvides as a Research Foundation - Flanders (FWO)-funded doctoral fellow. In 2012, he joined the Division of Structural Biology (STRUBI) at the University of Oxford (UK) as an EMBO- and Marie Curie Actions-funded postdoctoral fellow. There, he transitioned into molecular neuroscience and investigated the structural biology of synaptic protein complexes in the lab of Prof. A. Radu Aricescu.

General objective

The interests of our team are at the interface of structural biology, protein engineering, and molecular neuroscience. We aim to understand principles of neuronal signalling in health and disease, and to translate these to the cellular and organismal level.

We use mammalian protein expression, protein chemistry, biophysical methods, X-ray crystallography and cryo-electron microscopy to study the interaction determinants and structures of synaptic protein complexes involved in neurodevelopmental disorders and neuronal disease. We use combinatorial methods and protein engineering to discover novel binders and manipulate protein sequence, structure and function, to facilitate structural studies as well as enable therapeutic targeting of these complexes.

Expertise

  • Protein chemistry
  • X-ray crystallography
  • Biophysical analysis of protein-protein interactions
  • Molecular biology
  • Protein engineering
  • Yeast surface display
  • Mammalian protein expression
  • News

    Synthetic excitatory synaptic organizer - Science, August 2020

    A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

    The human brain contains trillions of synapses within a vast network of neurons. Synapse remodeling is essential to ensure the efficient reception and integration of external stimuli and to store and retrieve information. Building and remodeling of synapses occurs throughout life under the control of synaptic organizer proteins. Errors in this process can lead to neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements of natural synaptic organizers to develop an artificial version called CPTX, which has different binding properties (see the Perspective by Salinas). CPTX could act as a molecular bridge to reconnect neurons and restore excitatory synaptic function in animal models of cerebellar ataxia, familial Alzheimer’s disease, and spinal cord injury. The findings illustrate how structure-guided approaches can help to repair neuronal circuits.

    Authors: Kunimichi Suzuki, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Keiko Matsuda, 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

    - Science, 28 Aug 2020: Vol. 369, Issue 6507, eabb4853 - DOI: 10.1126/science.abb4853
    - Contact: Jonathan Elegheert

    Selected Publications

  • 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.
  • A synthetic synaptic organizer protein restores glutamatergic neuronal circuits Science (2020)
    MORE

  • Connor SA, Elegheert J, Xie Y, Craig AM.
  • Pumping the brakes: suppression of synapse development by MDGA-neuroligin interactions Current Opinion in Neurobiology (2019)
    MORE

  • Elegheert J, Behiels E, Bishop B, Scott S, Woolley RE, Griffiths SC, Byrne EFX, Chang VT, Stuart DI, Jones EY, Siebold C, Aricescu AR.
  • Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins Nature Protocols (2018)
    MORE

  • Elegheert J, Cvetkovska V, Clayton AJ, Heroven C, Vennekens KM, Smukowski SN, Regan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR.
  • Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins Neuron (2017)
    MORE

  • Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR.
  • Structural basis for integration of GluD receptors within synaptic organizer complexes Science (2016)
    MORE

    Members

    « Researcher »

    ELEGHEERT Jonathan Researcher jonathan.elegheert@u-bordeaux.fr +33533514858

    « Technical Staff »

    BEHIELS Ester Technical staff ester.behiels@u-bordeaux.fr +33533514858

    « Postdoc »

    RAUX Brigitt Postdoc brigitt.raux@u-bordeaux.fr +33533514700

    Jobs

    2 ERC-funded postdoctoral research positions

    2 ERC-funded postdoctoral research positions are available immediately to study the structure and therapeutic targeting of neuronal cell-surface receptors and protein complexes.

    The projects will involve mammalian protein production, protein chemistry, biophysical interaction analysis, X-ray crystallography, cryo-EM and discovery of Nanobodies (Nbs).

    The candidate(s) must hold a PhD degree and have less than two years of post-doctoral experience at the start of the contract. The candidate(s) should have a solid background in molecular biology, biochemistry and/or structural biology. Experience with (i) mammalian expression systems (HEK293 cell lines), (ii) biophysical analysis methods (surface plasmon resonance, isothermal titration calorimetry, microscale thermophoresis, etc.), and (iii) X-ray crystallography or cryo-EM, is preferred. The candidate should be highly motivated, a team player, and have a can-do problem-solving attitude.

    The project will be carried out under the supervision and mentorship of Dr. Jonathan Elegheert at the IINS in Bordeaux, France, which is recognised for its expertise in molecular and cellular neuroscience, and which is further embedded within the Bordeaux Neurocampus, a vibrant community of more than 700 neuroscientists.

    For project details and all other inquiries, please contact;

    Dr. Jonathan Elegheert
    E-mail : jonathan.elegheert@u-bordeaux.fr
    Tel : +33-(0)5.33.51.48.57

    Fundings

    Funding