Nicotinic acetylcholine receptors (nAChRs) are neurotransmitter-gated ion channels playing a major role in the nervous system. Their dysfunction is linked to severe psychiatric and neurological diseases such as nicotine addiction, schizophrenia or Alzheimer’s disease. Their architecture, allosteric mechanisms and pharmacology have been extensively studied over the last decades. However, the intracellular regulation of neuronal nAChRs is barely described. Yet, to achieve their physiological role, neuronal nAChRs are targeted to specific sub-cellular compartments through interaction with cytoskeleton-associated or synaptic proteins, and their function is further tightly regulated by intracellular factors. While key protein partners have been identified for other receptors such as the glycine, the GABAA or the glutamate receptors, little is known about the interactome of neuronal nAChRs.
We are looking for a highly motivated post-doctoral fellow to conduct an integrative structural biology approach to identify and investigate the complexes formed by neuronal nAChRs with their intracellular partners. The project combines cellular biology, biochemistry, and cryo-electron microscopy.
Expected profile:
- The applicant should have a PhD in biochemistry or structural biology.
- The applicant should have a strong experience in cryo-EM or crystallography AND/OR in eukaryotic or membrane protein biochemistry.
- The applicant should be motivated to apply for fellowship to extend the 1-year funding available
- The applicant should demonstrate her/his ability to work in collaboration with other team members.
The proposed research will be supervised by Dr Marie Prevost (https://research.pasteur.fr/en/member/marie-prevost/) and hosted by the Channel-Receptors Unit (headed by Pierre-Jean Corringer) of the Institut Pasteur (Paris, France). The Institut Pasteur offers an excellent scientific environment with several protein biology facilities, including a cryo-EM center equipped with two 200kV microscopes and a 300kV Titan microscope.
Applications including a CV and references contacts should be sent to marie.prevost@pasteur.fr.
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Relevant references from the host lab
Prevost, MS., Barilone N, Dejean de la Bâtie G, Pons S, Ayme G, England P, Gielen M, et al. ‘An Original Potentiating Mechanism Revealed by the Cryo-EM Structures of the Human Α7 Nicotinic Receptor in Complex with Nanobodies’. Nature Communications 14, no. 1 (25 September 2023): 5964. https://doi.org/10.1038/s41467-023-41734-4.
Li Q, Nemecz Á, Aymé G, Dejean De La Bâtie G, Prevost MS, Pons S, et al. Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor. Cell Mol Life Sci 2023;80:164. https://doi.org/10.1007/s00018-023-04779-8.
Nemecz A, Prevost MS, Menny A, Corringer P-J. Emerging Molecular Mechanisms of Signal Transduction in Pentameric Ligand-Gated Ion Channels. Neuron 2016;90:452–70. https://doi.org/10.1016/j.neuron.2016.03.032