CRN2M - UMR 7286

Center for Research in Neurobiology and Neurophysiology of Marseille

Director : Alain ENJALBERT

Faculté Médecine campus Nord
51 Bd Pierre Dramard
CS80011
13344 Marseille CEDEX 15
France

The Center for Research in Neurobiology and Neurophysiology of Marseille (CRN2M) associates 8 teams from the medical and the scientific components of Aix Marseille University. We are developing research projects in 4 major topics :

  1. Neurobiology
    Roles of ion channels in somatic and visceral sensitivity. Mechanism of ion channel targeting to neuronal compartment. Neuron-glia interactions and synapse plasticity. Visceral information processing.
  2. Cellular biology
    Neuronal polarity mechanism.
  3. Neuro-endocrinology
    Transcription factors. Clock genes. Intracellular signals and their implication in physio-pathology (pituitary development; neuroendocrine tumors).
  4. Neuro-immunology
    Neuroimmune interactions in neurodegenerative diseases.

These researches are conducted at the molecular, cellular and physiological levels, to implement our knowledge and to develop new therapeutic tools and diagnostic approaches through the interface with hospital departments.

These interfaces cover several important areas in terms of public health, such as somatic and visceral pain, respiratory pathologies, neuroimmune, demyelinating and neurodegenerative diseases, as well as neuroendocrine disorders

The CRN2M also offers access to 4 technology platforms:

  • Center for Microscopy and Imaging
  • Marseille Center for Proteomics
  • Transgenesis Center
  • Quantitative qPCR service

Pictures from the CRN2M laboratory

The research teams

All CRN2M teams are affiliated to the neuroscience master’s program and can thus train neuroscience master’s students and offer them projects to apply for a Ph.D. scholarship.

SIG-NET : SIGnalling in NeuroEndocrine Tumors (Anne Barlier)

We study the nature and mechanisms of signaling events in order to identify the key components controlling hormonal secretion and cell proliferation in neuroendocrine tumors and in meningiomas. Signal pathway is explored by land scale proteomic approaches from human tumors or cell lines. Data generated from proteomic approaches are integrated and modelled to identify bona fide molecular markers and understand key cellular signaling processes leading to predict effective combinatorial treatments. All the predictions are validated on cell lines and human tissues.

Our research is led with strong interaction with pharmacological industry to test new therapeutic molecules.

Members

Anne Barlier, Jean-Louis Berger-Lefranc, Thomas Cuny, Céline Defilles, Henri Dufour, Alain Enjalbert Corinne Gérard, Christophe Lisbonis, Pauline Romanet, David Romano, Alexandru Saveanu, Sylvie Thirion. Total : 3 HDRs.

Research axes

Transduction pathway in neuroendocrine tumours  (pituitary and gastro-entero-pancreatique tumours) and meningiomas.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Pharmacology
  • Bioinformatics

Keywords

Cancer, neuroendocrine tumors, pituitary, signaling, hormone secretion, cell proliferation, therapy, receptors, somatostatin, dopamine, interactome, protéomique

Disorders of the nervous system - Sleep, autonomic and neuroendocrine systems

Neuroimmune interactions and nervous system pathologies (José Boucraut)

We seek to define how changes in neuroimmune processes may either protect or alter nervous system pathophysiology. We use models of neuroinflammatory, neurodegenerative and psychiatric diseases, as well as in vitro, ex vivo and in vivo molecular and cellular approaches. Our perspective consists in proposing biomarkers for the diagnostic and the therapeutic follow-up of pathologies.

Members

José Boucraut, Raoul Belzeaux  Alexandre Brodovitch, Julia-Lou Consoloni, Emilien Delmont, Mylène Hervé, Anne-Michèle Hubert, El Chérif Ibrahim, Florence Pelletier, Natalia Popa, Gilda Raguenez. Total: 3 HDRs.

Research axes

  • Studies of RAE-1, CD1 molecules and NK, NKT cells in the physiology and pathologies of the nervous system
  • Role of proliferative microglia
  • Modeling molecular mechanisms underlying familial dysautonomia
  • Identification of blood biomarkers for the major depressive episode and schizophrenia

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Animal surgery, stereotaxy
  • Medical data analysis

Keywords

Immune system, lymphocytes, microglia, neuro-inflammatory diseases, neurodegenerative diseases, familial dysautonomia, major depression, schizophrenia, biomarkers

Disorders of the nervous system

Roles of transcription factors and clock genes in pituitary pathophysiology (Thierry Brue)

Our group studies the role of transcription factors and their mechanisms of action in the physiology and pathophysiology of the pituitary, and the molecular mechanisms involved in the development of circadian rhythms of pituitary hormones.

1. Physiopathology of the pituitary gland

In relation with a large multicentric clinical network aimed at the study of human hypopituitarisms of genetic origin and coordinated by T. Brue, we screen transcription factor genes involved in pituitary development (Hesx1, Lhx3 and 4, Pitx1 and 2, Prop1, Pou1F1/Pit1, Tpit, etc) for new mutations that might be responsible for pituitary deficits. The functional consequences of identified mutations are evaluated using in vitro approaches (DNA binding, transactivation of known target promoters, subcellular localization). For pituitary deficits of unknown etiology, we are trying to identify new genes whose mutations could be responsible for these deficits, using a “candidate gene” approach and/or genetic approaches.

2. Molecular mechanism of pituitary hormonal rhythm

Circadian rhythmic activity of the anterior pituitary gland is an essential component of the physiology of the gland. Studies conducted in our team showed that hormone rhythms could be generated locally and identified a role in the control of rhythmic gene expression for a long non-coding RNA, Neat1, the structural element of a nuclear compartment, the paraspeckles.
Our project aims to pursue the functional characterization of Neat1 in post-transcriptional mechanisms that allow the rhythmic expression of pituitary genes. We will then determine the importance of this mechanism in the functioning of the pituitary circadian oscillator: we will evaluate its contribution to the rhythmic transcriptome in the pituitary gland. We also will determine whether common RNA sequences may be found in genes whose rhythmic pattern involves Neat1.

Members

Thierry Brue, Denis Becquet, Bénédicte Boyer, Frédéric Castinetti, Alain Enjalbert  Teddy Fauquier, Jean-Louis Franc, Anne-Marie François-Bellan, Séverine Guillen, Jean-Paul Herman, Nicolas Jullien, Mathias Moreno, Marie-Hélène Quentien, Rachel Reynaud, Manon Torres. Total: 5 HDRs.

Equipe Brue, CRN2M

Research axes

  • Physiopathology of the pituitary gland
  • Molecular mechanism of pituitary hormonal rhythm

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Bioinformatics

Keywords

Transcription factors, pituitary, circadian rhythms, development, mutations, hypopituitarism, post transcriptional regulation

Animal cognition and behavior - Disorders of the nervous system - Sleep, autonomic and neuroendocrine systems

Axonal Domain Architecture (Bénédicte Dargent)

The axonal initial segment (AIS) is a unique sub-domain that plays a central role in the physiology of the neuron. It orchestrates both electrogenesis and the maintenance of neuronal polarity and the AIS is capable of homeostatic plasticity through an activity –dependent change in either its location or morphology.

Research axes

The goal of our work consists in deciphering the complex and dynamic mechanisms accounting for the assembly and the maintenance of the AIS, both in vivo and in cultured hippocampal neurons. Finally, the role of these mechanisms in AIS plasticity is also actively explored.

Members

Bénédicte Dargent, Ghislaine Caillol, Francis Castets, Claire Debarnot, Christophe Leterrier, Marie-Jeanne Papandreou, Fanny Rueda-Boroni. Total : 2 HDRs.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology or flow cytometry
  • Microscopy

Keywords

Axonal initial segment, neuronal domains, electrogenesis, neuronal polarity, plasticity

Development of the nervous system - Excitability, synaptic transmission, network functions

Ion Channels and Sensory Transduction (Patrick Delmas)

We are interested in sensory neurons that translate thermal, chemical, and mechanical stimuli. Our goal is to understand the molecular basis of somatosensation, with an emphasis on identifying molecules that regulate electrogenesis of sensory neurons and detect environmental stimuli. Our research also focuses on characterizing the function of the enteric nervous system in both gastroenterological and neurological disorders. Our group combines gene targeting, electrophysiology, histological methods and behavioral approaches to explore the channels, receptors and regulatory pathways that control sensory neuron functions. Genetic and physiological evidence from our lab suggests that Nav1.9 sodium channels are important players of the signaling mechanisms through which inflammatory mediators depolarize sensory neurons to produce pain hypersensitivity and neurogenic inflammation. We also study new mechanosensitive ion channels that detect gentle movement as well as noxious mechanical stimulation of the skin. We are working towards understanding the mechanism of activation of these channels under normal and pathological conditions, and we aim at identifying additional sensory-specific ion channels. Our lab is building on these studies to extend our knowledge of the molecular processes that control neuronal sensory-transduction and electrogenesis. On a related front, we are developing potent and selective inhibitors for sensory ion channels as potential antalgic agents. Our long-term goal is to synthesize an integrated picture of sensory neuron function. Our findings yield insights into the basic biology of the peripheral nervous system and have an impact on novel treatments for sensory diseases and pain.

Members

Patrick Delmas, Muriel Amsalem, Caroline Bonnet, Valentine Bouvier, Lucie Brosse, Bertrand Coste, Marcel Crest, Jean-Philippe Dales, Axel Fernandez, Jizhe Hao, Bruno Mazet, Yasmine Mechioukhi, Nancy Osorio, Françoise Padilla, Virginie Penalba, Jérôme Ruel, Linda Volkers, Ingrid Julien-Gau. Total: 2 HDRs.

Research axes

Ion channels, sensory system, mechanosensation, pain and pain headache, migraine.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology
  • Flow cytometry
  • Microscopy
  • Calcium imaging
  • Electropysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Optogenetics
  • Bioinformatics

Keywords

Sensory neurons, electrogenesis, sensory neurons, enteric nervous system, ion channels, mechanosensation, nociception, inflammation, pain, migraine, skin, inhibitors, analgesics

Animal cognition and behavior - Development of the nervous system - Excitability, synaptic transmission, network functions - Sensory systems

Neuron-glia interactions and neuropathology (Catherine Faivre-Sarrailh)

In myelinated axons, the action potentials are rapidly generated at nodes of Ranvier. The nodal gap contains high densities of voltage-gated sodium Nav1.6 channels. In addition, voltage-gated potassium channels Kv1.1/1.2 are clustered at juxtaparanodes and regulate axonal excitability.

The architecture and function of the nodes of Ranvier depend on several specialized zones of axo-glial contacts, the nodes, paranodes and juxtaparanodes. Our studies provide new insights into the mechanisms regulating surface targeting, and clustering of ion channels and cell adhesion molecules (CAMs).

Alterations of axonal domain organization are associated with demyelinating neuropathies and participate to conduction and excitability defects. We recently identified nodal and paranodal CAMs as primary targets of autoantibodies in peripheral neuropathies. We are determining how these autoantibodies are pathogenic by preventing cell adhesion, mediating disruption of the nodes and conduction loss.

We also focus on Caspr2, a CAM associated with Kv1, which is an autoimmune target in limbic encephalitis. In addition, the gene coding for Caspr2 is associated with neuropsychiatric disorders such as autism spectrum disorders, schizophrenia or language impairments.

Another topic developed in our lab is the study of neuron-glia interactions in Huntington’s disease, a neuropathology resulting from increased length of a polyglutamine stretch in the Huntingtin protein. We combine advanced genetic approaches in Drosophila with cellular analyses on primary cultured neurons. Our aim is to understand how glia contributes to energetic defect and abnormal neurotransmission in the disease.

Members

Catherine Faivre-Sarrailh, Marie-Thérèse Besson, Bruno HIVERT. Total: 2 HDRs.

Research axes

Role of the cell adhesion molecules in organizing axonal domains.
Cell adhesion molecules as target in autoimmune neuropathies
Drosophila models of Huntington disease, alteration of energy metabolism and mitochondria

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Genetics

Keywords

Nodes of Ranvier, neuron-glia interactions, membrane addressing, ion channels, adhesion molecules, demyelinating neuropathies

Disorders of the nervous system - Excitability, synaptic transmission, network functions

Gliotransmission & synaptopathies (Jean-Pierre Mothet)

Our ‘Gliotransmission and Synaptopathies’ team aims to uncover the functional relevance of glia-neuron interactions in the healthy and pathological brain with a special focus on the role of D-serine (an atypical amino acid essential for synapses) and other gliotransmitters in regulating chemical synapses. Our research plan is to:

  • Decipher the cellular and molecular mechanisms underlying gliotransmission and its mode of regulation
  • Study the function of gliotransmission and D-serine at glutamatergic synapses and in regulating the patterning and dynamics of neuronal networks in the hippocampus, the prefrontal cortex
  • Develop novel technological tools to study D-sérine

We address those challenges using a multidisciplinary and bottom-up approach of biochemistry, cell biology, electrophysiology and live imaging tools applied to dissociated glial and neuronal cultures, brain slices and in situ preparations. We work at advancing the frontiers on the functions of brain D-amino acids and glia in synaptic physiopathology with strong efforts to translate bench work to brain therapy and with the goal of developing novel technologies.

Members

Jean-Pierre Mothet, Sandrine Conrod, Matildé Le Bail, Grégoire Mondielli, Andrzej Bialowas. Total: 1 HDR.

Research axes

  • To decipher the cellular and molecular mechanisms underlying gliotransmission and its regulation.
  • To study the function of gliotransmission and D-serine at glutamatergic synapses and in regulating the patterning and dynamics of neuronal networks in the hippocampus, the prefrontal cortex.
  • To develop novel technological tools to study D-serine

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Pharmacology

Keywords

D-serine, gliotransmission, NMDA receptors, glia-neuron interactions, synapse, synaptic plasticity, exocytosis, neuromodulation

Excitability, synaptic transmission, network functions

Integration of visceral informations (Fabien Tell)

The team is studying the cellular mechanisms involved in the processing of sensory information coming from the viscera. With cellular approaches, we study the synaptic physiology and the electrical properties of neurons located at the first integration center for visceral information, the nucleus of the solitary tract. This work feeds more integrated studies aimed at deciphering the operation of circuits controling homeostatic regulation (breathing, digestion…).

Members

Fabien Tell, Michelle Bevengut, Olivier Bosler, Christian Gestreau, Caroline Strube. Total: 4 HDRs.

Research axes

  • Organization of neurotransmission in the nucleus of the solitary tract (NTS), the major entry to the brain for viscero-sensory information.
  • Neural circuits involved in the regulation of respiration and movement of the upper airway.
  • The effects of an air pollutant, ozone, on brain structures involved in stress responses.

Techniques

  • Biochemistry
  • Immunostaining, histology
  • Flow cytometry
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Bioinformatics

Keywords

Sensory information, viscera, nucleus of the solitary tract, circuits, homeostatic regulation, respiration, digestion, ozone, stress reactions

Excitability, synaptic transmission, network functions - Motor systems - Sleep, autonomic and neuroendocrine systems
Share the article on :