IBDM - UMR 7288

Developmental Biology Institute of Marseille

Director : André LE BIVIC

Campus Luminy
case 907
13288 Marseille CEDEX 9
France

IBDM is an interdisciplinary research institute oriented towards developmental biology and pathologies.

Half of its twenty teams addresses biological questions related to the nervous system development, maturation and plasticity. Unraveling these processes is essential to understand the pathogenesis of neurological disorders and design novel therapeutic targets.

The institute encompasses complementary scientific approaches including experimental embryology, physiology, cellular/molecular biology, genetics, biocomputing and genomics.

Using a large spectrum of animal models, IBDM research effort in Neurosciences focuses on neural stem cell biology, cell fate determination, cell division and migration, axon guidance and circuit formation, neuroplasticity in the normal adult brain and adaptive changes in disease states.

The scientific equipment is grouped into innovative and effective technical platforms, including state of the art imaging center, animal housing and functional exploration facilities. One of the key objectives of the IBDM is to encourage interaction with different disciplines –mathematics, physics, chemistry – in order to develop new experimental approaches.

In addition to basic research, IBDM promotes projects in the field of applied science, aimed at developing therapeutic molecules. Furthermore, in collaboration with the university, the institute plays an important role in developing teaching programmes in biology and at the interface between biology and other disciplines.

Pictures from the IBDM laboratory

Research teams

Three IBDM teams are affiliated to the neuroscience master’s program :

  • Stem cells and brain repair
  • Cellular interactions, neurodegeneration and neuroplasticity
  • Functional significance of primary sensory neurons diversity

Only these 3 teams can thus train master’s students and offer them projects to apply for a Neuroscience Ph.D. scholarship.

The other teams are affiliated to other master’s programs.

Stem cells and brain repair (Pascale Durbec)

The team focuses on the process of post-lesional plasticity following demyelination in the adult brain. In some patients affected by multiple sclerosis (MS) spontaneous remyelination can occur. Although insufficient to counter the damages caused by the repetitive attacks, this spontaneous regenerative process represent great therapeutic hopes. Studies led on rodent have identified two distinct sources of cells involved in remyelination: the oligodendrocyte progenitors (OPCs) found throughout the brain parenchyma and neural progenitor derived from the sub-ventricular zone (SVZ) were adult neural stem cells reside.

Our objectives are to uncover the cellular and molecular mechanisms controlling this process in order to increase our fundamental knowledge on brain regeneration and to promote myelin repair.

Members
Pascale Durbec, Myriam Cayre, Claire Bertet, Karine Magalon, Bilal El Waly, Béatrice Brousse, Léa Le Poder . Total : 2 HDRs.

Research axes

  1. The cellular and molecular control of myelin formation and regeneration in the adult rodent brain.
  2. The contribution of adult stem cells to brain repair.
  3. The mechanisms that regulate oligodendrocytes migration and differentiation.
  4. The research and preclinical evaluation of new therapeutic strategies for myelin repair in patients suffering from multiple sclerosis.

Techniques

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

Keywords

Adult stem cell, migration, myelin, neurodegeneration, oligodendrocyte, plasticity, remyelination, multiple sclerosis, experimental models, experimental therapeutics

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system

Cellular interactions, neurodegeneration and neuroplasticity (Lydia Kerkerian)

The team studies cellular interactions and neuroplasticity in the adult brain, in particular in the context of basal ganglia-related functions and pathologies.

Ongoing projects are centered on the pathophysiology and treatment of Parkinson’s disease and the role of glutamatergic systems.

Our approach combines the use or development of relevant experimental models in rodents (chronic deep brain stimulation, genetic model of cell specific ablation, optogenetic modulation of neuronal activity) with a variety of analytic tools including functional anatomy, electrophysiology (in vitro and in vivo), neurochemistry and molecular/cellular biology.

Members

Lydia Kerkerian-Le Goff, Corinne Beurrier, Dorian Chabbert, Paolo Gubellini, Marwa Hanini, Florence Jaouen, Philippe Kachidian, Sylviane Lortet, Nicolas Maurice, Christophe Melon, André Nieoullon, Pascal Salin. Total : 5 HDRs.

Research axes

  1. The anatomofunctional organization of the basal ganglia network and its remodeling in Parkinson’s disease
  2. The cellular/molecular bases of the beneficial or side-effects of the current treatments for Parkinson’s disease
  3. The research and preclinical evaluation of new therapeutic strategies
  4. The cell death mechanisms, with focus on those linked to dysfunction of glutamate transporters

Techniques

  • Molecular biology
  • Biochemistry
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Electrophysiology (on slices or cells)
  • Electrophysiology (in vivo)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Optogenetics
  • Deep brain stimulation

Keywords

Neuroplasticity, basal ganglia, Parkinson’s disease, experimental models, experimental therapeutics, dopamine, glutamate, excitotoxicity, neurodegeneration, physiopathology

Animal cognition and behavior - Disorders of the nervous system - Excitability, synaptic transmission, network functions - Motor systems - Novel methods and technology development

Functional significance of primary sensory neurons diversity (Aziz Moqrich)

Our team aims at understanding how primary sensory neurons diversity is translated at the functional level. To do this we use state-of-the-art technologies combining mouse genetics, transcriptomic analyses, molecular and cellular biology, electrophysiology and behavior.  In the last few years we successfully contributed to extend our understanding of the molecular logic that governs nociceptive neurons diversity, we unraveled the functional role of newly identified genes in pain biology and deciphered the functional specialization of two newly characterized subpopulations of primary sensory neurons. Currently, our projects are heading towards a better understanding of the circuitry between primary sensory neurons and spinal cord neuronal networks. We are also developing clinically-driven projects in which we investigate the molecular and cellular mechanisms that underlie the transition from acute to chronic pain.

Members

Aziz Moqrich, Serge Alonso, Manon Bohic, Eduardo Gascon, Pascale Malapert, Irène Marics, Ana Reynders, Catarina Santos. Total : 2 HDRs.

Research axes

  1. Primary sensory neurons diversity
  2. Role of DRG neurons subset in pain sensation
  3. Dicephiring the circuitry between C-LTMRs and laminae IIi interneurons
  4. Molecualr and cellular mechanisms underlying the transition from acute to chronic pain

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Calcium imaging
  • Electrophysiology (on slices or cells)
  • Animal surgery, stereotaxy
  • Pharmacology
  • Animal behavior
  • Optogenetics
  • Bioinformatics
  • Mouse genetics

Keywords

Primary sensory neurons, neuronal circuits, behavior, pain, disease, neurogenesis, transgenic mice.

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

Polarization and binary cell fate decisions in the nervous system (Vincent Bertrand)

In both vertebrates and invertebrates, postmitotic neurons are often generated by asymmetric divisions of neuronal progenitors such as neural stem cells. This general mechanism used to build the nervous system raises two important questions : how are these asymmetric divisions coordinated in space and how do the daughter cells acquire different fates.

We address these questions using the nematode C. elegans as a model organism. In C. elegans, most neurons are generated during neurulation by asymmetric divisions oriented along the antero-posterior axis. We recently showed that these terminal asymmetric divisions are regulated by a particular Wnt/β-catenin pathway. We are now trying to understand :

1) How the field of neuronal precursors is polarized.

2) How the daughter cells acquire different fates and especially how the asymmetric division machinery is connected to the terminal differentiation program of postmitotic neurons.

The Wnt/β-catenin pathway is involved in several types of cancer and in the regulation of asymmetric divisions of neural stem cells in vertebrates. This study may therefore help identify candidate target proteins and mechanisms for future anti-cancer drug developments or regenerative medicine treatments.

Members

Vincent Bertrand, Antoine Barriere, Guillaume Bordet, Carole Couillault, Shilpa Kaur, Sabrina Murgan. Total : 1 HDR.

Research axes

  1. Polarization mechanism of a neuronal precursor field
  2. Role of the Wnt pathway in the specification of neuronal subtype identities
  3. Role of chromatin factors in neuronal differentiation
  4. Evolution of the mechanisms of neuronal specification

Techniques

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

Keywords

Advanced in vivo imaging, asymmetric division, Caenorhabditis elegans, gene regulation, neurogenesis, neuronal precursors, stem cell, tissue polarity, Wnt signaling

This team is not affiliated to the Neuroscience Master’s.

Development of the nervous system

Molecular control of neurogenesis (Harold Cremer)

Neurogenesis in the olfactory system

In defined regions of the mammalian brain neurogenesis proceeds into postnatal and adult stages. One example for such ongoing neurogenesis is the subventricular zone (SVZ) of the forebrain lateral ventricles. There, pre-determined neuronal stem cells generate large amounts of neuronal progenitors. After their amplification, these young neurons perform long distance chain migration within the rostral migratory stream into the olfactory bulb, where they differentiate into interneurons that use GABA, dopamine and glutamate as their neurotransmitter.

Using this experimental system, we developed new strategies in order to identify and functionally analyze factors regulating neurogenesis in a systematic and efficient manner. We performed a series of high resolution genetic screens to gain profound insights into gene and microRNA expression in the system in space and time. In parallel, we developed a new method that allows easy and targeted electroporation of transgenes and inhibitory shRNAs into defined neural stem cells in the postnatal and adult SVZ, thereby permitting efficient functional in vivo analyses.

Members

Harold Cremer, Alexandra Angelova, Christophe Beclin, Stéphane Bugeon, Nathalie Coré-Polo, Antoine De Chevigny, Mathilde Hevers, Sahra Lafi, Jean-Claude Platel, Marie-Catherine Tiveron Rousselin, Laetitia Weinhard, Thibault Ganay. Total : 4 HDRs.

Research axes

  1. How are neural stem cells along the ventricular wall determined to produce neurons with defined neurotransmitter phenotypes, morphologies and connectivity?
  2. How is long distance migration of neuronal progenitors controlled?
  3. How is terminal neuronal differentiation and integration in the olfactory bulb regulated?
  4. How are new synapses induced and stabilized in the adult brain?

Techniques

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

Keywords

Adult neurogenesis, cell therapy, dopaminergic neurons, in vivo electroporation, microRNAs, neurogenesis, Parkinson’s disease, stem cell, transgenic mice

This team is not affiliated to the Neuroscience Master’s.

Development of the nervous system - Disorders of the nervous system

Molecular mechanisms underlying mesenchymal cell differentiation (Laurent Fasano)

Teashirt3 (TSHZ3) is a zinc finger transcription factor whose targets and functional implications remain largely unknown. Our previous studies support that Tshz3 plays a role in the developing and maturing cerebral cortex. To unravel the role of Tshz3 in the development and function of cortical projection systems, we are characterizing novel mouse models of Tshz3 deletion by combining mouse genetics, molecular biology, morphological and tract tracing studies, slice electrophysiology and behavioral approaches. This research will improve our knowledge on mechanisms underlying early corticogenesis and/or maturation and functioning of cortical circuits.

Members

Laurent Fasano, Xavier Caubit, Ahmed Fatmi, Laurence Had-Aissouni, Dimitri Stojanovic, Irene Sanchez-Martin. Total : 3 HDRs.

Techniques

  • Molecular biology, in situ hybridization
  • Biochemistry
  • Cell culture
  • Immunostaining, histology
  • Microscopy
  • Animal behavior
  • Bioinformatics

Keywords

Behavior, transcriptional control, corticogenesis, development, differentiation, neuronal identity, disease, morphogenesis, visceral smooth muscle, cortical neurons, gene regulation

This team is not affiliated to the Neuroscience Master’s.

Animal cognition and behavior - Development of the nervous system

Development and pathologies of neuromuscular circuits (Françoise Helmbacher)

The Helmbacher team studies neuromuscular development and pathology. Our research aims to understand processes that control the development of neuromuscular circuits, and to uncover how alterations of these developmental processes lead to devastating neuromuscular pathologies in human. Our work on neuromuscular development integrates the study of cell fate diversity and the mutual dependency of motor neurons and their target muscles. We aim to identify the signals successively exchanged by neurons and muscles during development, such as the signals acting on neuronal and muscular specification, the signals that pattern neural projections through axonal guidance and through muscle morphogenesis, the signals that regulate homogeneous growth and match the size of neuromuscular units. We study how all these signals successfully integrate to produce locomotor activity.

Our work recently uncovered the link between a human myopathy, Facioscapulohumeral dystrophy, and genetic alterations of the FAT1 cadherin gene, a gene involved in neuromuscular development. We currently work at determining the contribution of FAT1-dependent phenotypes to FSHD-like muscular symptoms. Besides, we also explore how FAT/Dachsous cadherin signaling contributes to the functional maturation of neuromuscular circuitry.

Members 

Françoise Helmbacher, Magali Macchi, Dominique Fragano.

Research axes

  1. Mechanisms of neuromuscular circuit assembly
  2. Neuromuscular Fatopathies and FSHD (facioscapulohumeral muscular dystrophy) physiopathology
  3. Role of FAT/Dachsous signaling during functional maturation of neuromuscular circuits.

Techniques

  • Molecular biology
  • Cell culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Movement or posture analysis, electromyography (EMG)
  • Bioinformatics
  • Genetics (mouse models)

Keywords

Neural circuits, connectivity, neuromuscular development, muscular dystrophy, axon guidance, cell migration, adhesion molecule, morphogenesis, motor neuron, muscle, pathophysiology.

This team is not affiliated to the Neuroscience Master’s.

Development of the nervous system - Disorders of the nervous system

Signalling networks for stemness and tumorigenesis (Flavio Maina)

We aim at uncovering how convergent instructive signals cooperate to regulate the fate of cells. This question is addressed by using two biological contexts: the transition of healthy cells towards tumorigenesis and the regulation of self-renewal versus differentiation of stem cells.

Concerning stem cells, the team studies how human induced pluripotent stem cells (iPSCs) fine-tune perception of instructive extracellular signals in order to: 1) enhance generation of functional neurons (e.g. dopaminergic neurons) both in vitro and in vivo; 2) improve safety of human iPSC-derived cell grafts in animal models of neurodegenerative disorders (e.g. Parkinson’s disease) by preventing tumour side effects.

Our objective is to acquire knowledge on human iPSC biology related to neural/neuronal differentiation by exploring molecular and signalling networks. This research may open new perspectives in regenerative medicine by developing more effective, user-friendly, and safe stem cell-based therapeutic strategies (project leader Dr Rosanna Dono).

Membres

Flavio Maina, Rosanna Dono, Fabienne Lamballe, Maria Arechederra-Calderon, Fangyu Shi, Yannan Fan, Serena Corti, Sylvie Richelme. Total : 3 HDRs.

Research axes

  • Modelling receptor tyrosine kinase signalling in vivo to uncover cooperative signals in cancer.
  • Balancing stem cells self-renewal versus differentiation by modulating perception of instructive signals.
  • Signalling network crosstalk uncoupling tumorigenicity from therapeutic properties of human iPSCs.
  • Exploring mechanisms underlying neuronal differentiation (e.g. dopaminergic fate acquisition) during mouse embyogenesis and in human iPSCs.
  • Preclinical evaluation of human iPSCs-based therapy for neurodegenerative disorders, using Parkinson as disease model.

Techniques

  • Molecular biology
  • Biochemistry
  • Cell culture and embryo culture
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Animal behavior
  • Bioinformatics
  • Transgenesis
  • Xenografts

Keywords

Modelling tumorigenesis, receptor tyrosine kinase signalling in vivo, signalling modulation, glypicans, stem cells, human iPSCs, development, mouse genetics, neuronal differentiation, Parkinson’s disease, stem-cell based replacement therapy.

This team is not affiliated to the Neuroscience Master’s.

Animal cognition and behavior - Development of the nervous system - Disorders of the nervous system - Novel methods and technology development

Axon guidance in the mammalian brain (Fanny Mann)

The team studies axon guidance, a key step in the formation of neural circuits, and circuit remodeling in organs affected by cancer.

Axon guidance is the process by which neurons extend an axon to reach their targets. Our projects aim to decipher the mechanisms involved in guiding the development of axon tracts (commissures) that interconnect the left and right brain hemispheres. Our laboratory is particularly interested in a family of guidance molecules, called Semaphorins, and the molecular pathways that determine how neurons receive and interpret these signals. For example, an in-depth study of a member of this family, Sema3E, revealed that its repulsive or attractive action on axonal growth is determined by the composition and intracellular trafficking of the receptor complexes expressed by the axon.

In addition to their role in brain development, axon guidance molecules are frequently expressed in cancers. The team studies how these signals contribute to the infiltration of nerve fibers inside tumors, a process called tumor axonogenesis. This work should help to identify new therapeutic approaches targeting the nervous system to treat cancer.

Members

Fanny Mann, Sophie Chauvet, Mélanie Hocine-Ducros, Erik Miré, Thi Trang Huyen Nguyen, Theodora Velona, Jeremy Guillot. Total : 2 HDRs.

Research axes

  1. the cellular and molecular events leading to the formation of major axon tracts in the mammal brain
  2. the control of  guidance receptor trafficking by PDZ domain-containing molecules, often chosen as therapeutic targets in nervous system disorders
  3. the remodeling of neuronal projections and the role of axon guidance cues in cancers

Techniques

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

Keywords

Neurodevelopment, neuronal circuits, axon guidance, receptor trafficking, signaling, brain commissures, neurological disorders, cancer, tumor axonogenesis.

This team is not affiliated to the Neuroscience Master’s.

Development of the nervous system - Disorders of the nervous system

Neural stem cell plasticity (Cédric Maurange)

Neural stem cells found in the nervous system are very plastic. This plasticity allows them to generate a vast repertoire of neural and glial progeny while the brain is being built or to regenerate neurons after brain injury. Our team aims at deciphering the molecular and genetic mechanisms underlying this plasticity. We are also investigating how environmental conditions during fetal growth affect neural stem cell plasticity and their ability to constitute their full repertoire of neurons. Finally, because of their plasticity and large proliferation potential, stem cells are largely exposed to cancer-promoting defects. Our ambition therefore consists in uncovering how neural stem cell plasticity can be hijacked for the benefit of cancerous processes. Understanding these basic principles could help correcting cellular failures responsible for cancer induction, delaying ageing and exploiting neural stem cell regenerative potential.

In order to investigate these fascinating issues, we use the fruitfly Drosophila. As in mammals, the Drosophila adult brain is mainly composed of neurons and glial cells (>100,000) disposed in complex neural circuits. These cells have been generated in the developing animal from a limited set of neural stem cells. We take advantage of the powerful genetic tools developed in this model organism to manipulate neural stem cells while the brain is being constructed during development. We aim at identifying the genes and molecular mechanisms controlling their properties.

Members 

Cédric Maurange,  Caroline Eple, Sophie Foppolo, Cassandra Gaultier, Sara Genovese, Nuno Luis, Karine Narbonne-Reveau. Total : 1 HDR.

Research axes

  • to decipher how a genetic program is deployed in every neural stem cells to ensure that different types of neurons are generated over time
  • to investigate the impact of nutritional conditions on the making of the brain
  • to explore the mechanisms that drive tumour progression in a developing brain, as happens for pediatric neural cancers

Techniques

  • Molecular biology
  • Biochemistry
  • Immunostaining, histology, or flow cytometry
  • Microscopy
  • Bioinformatics

Keywords

Cancer, neural stem cell, cancer stem cell, neuronal specification, brain development, nutrition, paediatric cancer, Drosophila.

This team is not affiliated to the Neuroscience Master’s.

Development of the nervous system - Disorders of the nervous system
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