Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/polarization-and-binary-cell-fate-decisions-in-the-nervous-system/

Team leader : Vincent Bertrand

Research domain : Development, neurobiology, polarity, transcription

Contact : Vincent Bertrand - vincent.bertrand@univ-amu.fr

Our team is analyzing how the nervous system is built during animal development, and subsequently maintained during adulthood. To address this question we are using quantitative live imaging approaches and the invertebrate C. elegans as a model organism. More precisely, we are addressing two main questions:

1) Polarization of a field of neuronal precursor cells

Neurons are produced by the asymmetric divisions of neuronal precursor cells. We are trying to understand how the divisions of the neuronal precursors are regulated and coordinated in space. We have identified secreted ligands, receptors and intracellular transducers involved in this process. In collaboration with the team of Pierre-François Lenne (IBDM) we are currently using quantitative live imaging methods to analyze the dynamics of these molecular players during the polarization process in vivo. Interactions with modelers will be important in the future to integrate these quantitative data into a general model of tissue polarization.

2) Specification and maintenance of neuronal identity

A high diversity of neurons is generated during the development of an animal. These neurons subsequently maintain their identity throughout the life of the animal. Because defects would lead to the generation of an abnormal complement of neurons during development or to the progressive loss of some neuronal populations during aging, this process has to be strictly controlled. The identity of neurons is regulated by networks of transcription factors, but how these networks can ensure a reliable specification and maintenance of neuronal fate despite the noise present in gene expression and the variability in environmental conditions is unclear. To address this question we are using CRISPR based genome engineering approaches and live imaging to analyze the dynamics of a network of transcription factors involved in the regulation of neuronal cell fate. Collaborations with modelers will be important to build a model of this network and to better understand its response to perturbations such as physiological stresses.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/molecular-control-of-neurogenesis/

Team leader : Harold Cremer

Research domain : Development, neurobiology

Contact : Harold Cremer - harold.cremer@univ-amu.fr

Understanding neural stem cell diversity and differentiation at the molecular level: Genes and microRNAs

A key question in developmental neurobiology concerns the molecular mechanisms that control the specification of stem cells to produce neurons with defined neurotransmitter phenotype, positions and connectivity. Combinatorial expression of transcription factors, highly controlled in space and time, has been shown to underlie the determination events that lead to neuronal diversity. Historically these endogenous factors have been considered to act in an « all-or-nothing » fashion. However, it is now clear that many of these factors act highly dose-dependent.

Using adult neurogenesis in mice as the experimental model we found that small differences in transcription factor concentration in neighboring neural stem cells, fine-tuned by the superposed action of specific regulatory non-coding RNAs (microRNAs), lead to distinct neuronal fates. Moreover, neuronal fate decisions are not restricted to the stem cell compartment, but can occur at later stages of neuronal differentiation.

To systematically investigate the expression, interaction and function of mRNAs and microRNAs during adult neurogenesis in space (in different stem cell populations) and in time (from stem cells to neurons).

Based on our ability to genetically label and isolate defined neural stem cell populations and their entire lineages in vivo, we generated unique high-resolution gene- and microRNA expression data. While initial studies have been performed at the cell-population level - labeling defined stem cell pools and investigating their transcriptome/microRNome as a whole - it is now clear that we have to perform such analyses at higher resolution, using new technologies like single cell RNAseq.

Campus / location : Luminy

Website : https://www.ibdm.univ-amu.fr/team/epithelial-monolayer-morphogenesis/

Team leader : Delphine Delacour

Research domain : Epithelium – Intestine – Organoids – Tissue morphogenesis and integrity - Cytoskeleton

Contact : Delphine Delacour - delphine.DELACOUR@univ-amu.fr

Epithelia act as a physical barrier against external aggressions but also ensure organ functionality. If not correctly assembled or dysfunctional, this leads to pathological situations that include a variety of diseases spanning from rare developmental syndromes or cancer. How epithelia coordinate and harmonize the responses of each cell with not only their nearest neighbors, but entire tissue, to guarantee proper spatial arrangement, integrity and functionality is still not well understood. So far, the question of epithelial coherence has been mainly tackled in invertebrate models during development or in transformed cell lines in culture.

The intestinal epithelium is a tremendous model for this field of research, as it is one of the most fast-proliferative and regenerative in mammalian organisms. In addition, the intestinal tissue is subject to adverse situations, where the balance between cell proliferation, differentiation and death has to be strictly maintained. However, the study of the cellular and developmental mechanisms that govern the development and architecture of the intestinal tissue is still in its infancy.

The general objective of our project focuses on understanding the determination and maintenance of intestinal functional domains, and to evaluate their spatiotemporal coordination. More specifically, our aims are: 1) to define mechanisms controlling the integrity of the proliferative domain, and assess their impact on the crypt development; 2) to characterize the epithelial connectivity and collective behavior of the differentiated domain in homeostatic conditions or under challenging contexts.

One of the strong aspects of our research is to confront in vivo and in vitro murine and human disease models, and to combine different approaches from advanced cell biology, tissue engineering, histology, molecular biology, biophysics and computational modelling. This strategy allows us to determine the adaptive processes that epithelial cells employ to polarize and organize in a given environment, and enhance their ability to modulate their fate.

To know more:

1- Cryptogenesis

Research on intestinal crypts has mostly focused on stem cell asymmetric divisions in terms of fate or rate of proliferation. However, crypt morphogenesis by itself remains an understudied field of research. In recent studies, we have implemented intestinal organoid cultures, their high-resolution imaging and genetic manipulations to decipher the cryptogenesis process. We currently address mechanisms regulating the crypt organization, and their contribution to the development of rare intestinal diseases and cancers.

2- Epithelial organization and connectivity

How is ensured multicellular coordination in mammalian adult epithelia? We assess cell adhesion patterning and supracellular network emergence at the tissue level in vitro in organoid cultures and in vivo in mammalian tissues, and determine their spatiotemporal orchestration for epithelial connectivity.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/stem-cells-and-brain-repair/

Team leader : Pascale Durbec

Research domain : Neurobiology,  brain plasticity

Contact : Pascal Durbec - pascale.durbec@univ-amu.fr

Despite the existence of reservoir of stem cells and progenitors, the central nervous system shows really limited regenerative properties after lesion or in neurodegenerative conditions. An important issue in neuroscience is to characterize these stem/progenitor cell populations in physiological and pathological contexts and to design future cell based therapeutic strategies to promote brain regeneration. A spontaneous regenerative process involving the production of new mature oligodendrocytes (OLG) the myelin forming cells of the brain, has been observed after demyelination in Multiple Sclerosis patients. This process is rarely effective and the loss of myelin (demyelination) is accompanied by a disruption in the ability of the nerves to conduct electrical impulses to and from the brain. The objective of the team is to describe this regenerative process in rodent.

Stem and precursor cells of the adult Sub-ventricular zone (SVZ) are implicated in this spontaneous regenerative process. In physiological conditions, SVZ stem cells generate mainly neuronal progenitors, which migrate to the olfactory bulb, where they differentiate into interneurons. Several studies have shown that in demyelinating conditions, some SVZ-derived neuronal progenitors are mobilized and migrate toward lesions. This surprising observation changes our vision of cell commitment and raised important questions concerning post-lesional cell plasticity in the adult brain: how a cell committed to a specific lineage can change fate? Can neuronal progenitors generate OLG by transdifferentiation or do they need to first de-differentiate to change fate? What are the molecular mechanisms regulating this fate switch in the adult brain?

We have strong preliminary showing that a few days after demyelination, neuronal progenitors generate OLG through direct transdifferentation. Indeed, we observed around the lesion and in the SVZ a population of cells, that we called “the mixed entity”, expressing concomitantly both neuronal and OLG markers. Our objectives are to extend our knowledge on in vivo spontaneous cell transdifferentiation events by comparing the transcriptional signatures of the mixed entity to that of neuronal progenitors and of OLG in physiological conditions and after lesion. This analysis based on single cell transcriptomic analysis should provide insight into the molecular cascades controlling in vivo direct cell reprogramming.

In a short term, we will benefit from interaction with mathematicians to theoretically describe and model this cell reprogramming even. Based on single cell transcriptomic data, we could perform modeling and machine learning techniques for the analysis of gene regulatory networks to map the landscape between the dynamic cellular states identified during in vivo cell reprogramming and to model the genomic modifications due to lesion induction.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/molecular-mechanisms-underlying-mesenchymal-cell-differentiation/

Team leader : Laurent Fasano

Research domain : Developmental biology

Contact : Laurent Fasano - laurent.fasano@univ-amu.fr

As a developmental biologist, I aim to understand how cells initially identical become different by expressing different set of genes.

Decoding the temporal control of gene expression patterns is key to the understanding of the complex mechanisms that govern developmental decisions during organ/tissue development. My team has identified the teashirt (Tshz) genes family that encode evolutionarily conserved zinc finger transcription factor (TSHZ). Our research centres on understanding how TSHZ3-related transcriptional networks help cells taking on gradually a final identity within the context of normal and pathological development.

Recently, we identified TSHZ3 as the critical gene for a syndrome whose characteristic clinical manifestations are autism spectrum disorders and congenital anomalies of the kidneys.

To identify the key mechanisms that contribute to the initiation, development and maintenance of autistic-type phenotypes along the temporal axis we perform a multilevel study, from behaviour to molecule, using mouse models. At the molecular level, we use genome-wide expression profiling technologies (i.e. microarray and next-generation sequencing) to analyse spatio-temporal changes in gene expression in response to spatio-temporal targeted Tshz3 deletion experiments.

We need to perform integrative functional analyses to identify critical temporal windows and cell types that are key for ASD and/or kidney pathogenesis.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/mechanisms-of-gene-regulation-by-transcription-factors/

Team leader : Yacine Graba & Andrew Saurin

Research domain : Developmental biology

Contact : Yacine Graba - yacine.graba@univ-amu.fr ; Andrew Saurin - andrew.saurin@univ-amu.fr

The team activity is centered on the mechanisms of gene regulation by transcription factors in developmental and evolutionary processes, taking the study of Hox transcription factors as a paradigm. This is achieved by combining genomics and proteomics to set the molecular landscape, structural biology and molecular modeling to grasp the atomic details of the mechanisms, and classical molecular genetics to probe in vivo function. Past work has significantly remodeled our representation of Hox protein function, notably by the identification of the potential importance of flexible protein domain folding and plastic protein interactions for Hox transcription factor function. We believe this plasticity in interactions suits the capacity of Hox proteins to accommodate hundreds of regulatory regions and multiple protein partners, providing the molecular support for Hox protein functional diversity, specificity and evolvability.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/computational-biology/

Team leader : Bianca Habermann

Research domain : Developmental biology; Computational Biology

Contact : Bianca Habermann - bianca.habermann@univ-amu.fr

Computer-driven analysis has complemented biological research for a long time. With the beginning of sequencing and deciphering the genetic code, methods were develop that help analyze this type of data. The sequencing of parts of or entire genomes has for instance enabled us to establish a fine-tuned view on the evolution of species.

In recent years, large-scale screens and next generation sequencing is generating a tremendous amount of data, which cannot be analyzed – or understood – without the help of computational techniques. Our lab is working in computer-assisted analysis of biological data.

Our team works on two aspects in computational biology:

First, we want to make use of the vast amount of biological information available to date and put it into the perspective of biological systems in development or disease. We have chosen mitochondria to demonstrate the usefulness of large-scale data integration to understand a biological system. Mitochondria are the so-called power-houses of the cell. They provide not only energy to the cell, but are tightly involved in a multitude of metabolic functions in the cell. Their central role in cellular development and also homeostasis makes them a perfect target to investigate changes taking place in the mitochondrial system. We develop methods for the interpretation and integration of biological data and apply them to understand the – change of – function of mitochondria in a developing tissue or in a disease like Parkinson disease or cancer.

Second, we are working with protein sequence similarities in the so-called midnight zone: two related proteins have undergone so many mutations that it is difficult to detect the similarity in their sequence. We have developed methods for detecting remote homologs, remotely conserved functional domains, as well as remotely conserved orthologs – which depicts proteins that are directly evolved from each other. Currently, we are working on methods for the de novo prediction of short, functional motifs in proteins: can we, without any prior information, identify a short stretch of sequence in a protein, which performs a specific function, such as binding another protein or binding to a ligand? We are approaching this problem using either only the protein sequence or only its structure in three-dimensional space.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/genetic-control-of-heart-development/

Team leader : Robert G. Kelly

Research domain : Developmental biology

Contact : Robert G. Kelly - robert.kelly@univ-amu.fr

Our group is interested in understanding the genetic and cellular mechanisms underlying organogenesis of the four chambered mammalian heart. In particular we study an epithelial progenitor cell population known as the second heart field that gives rise to a large part of the heart by addition to the poles of the elongating heart tube in the early mouse embryo. Defects in the deployment of second heart field cells result in congenital heart defects. The second heart field is derived from a larger progenitor cell field that also gives rise to skeletal muscles of the head. Our group studies the mechanisms underlying patterning, differentiation and cell dynamics in this progenitor field, In addition, we are investigating the later development of a network of specialised conducting cell that regulate electrical activity in the ventricles.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/cellular-interactions-neurodegeneration-and-neuroplasticity/

Team leader : Lydia Kerkerian - Le Goff

Research domain : Neuroscience

Contact : Corinne Beurrier - corinne.beurrier@univ-amu.fr; Jean-Pierre Kessler - jean-pierre.kessler@univ-amu.fr

Our research activity is centered on the normal and pathological functioning of a network of brain structures called basal ganglia (BG), which plays a major role in motor control and whose dysfunction is associated with movement disorders, as in Parkinson’s disease.

Our physiological level of analysis of BG circuit function and dysfunction, which includes EEG, extracellular and intracellular electrophysiological recordings, would strongly benefit from collaboration with mathematicians to push forward signal analysis, especially when moving from single to multi-electrode/multi-unit recordings. Moreover, computational modeling of networks based on our anatomical and electrophysiological data is essential to understand BG dynamics both at structure level (e.g. local microcircuits in BG components, as the striatum, the main BG input station) and at system level (the BG network). For example, we are currently studying the physiological and pathological implications of a small population of striatal interneurons, the cholinergic interneurons, by combining optogenetics, to timely control their activity, with slice or in vivo electrophysiological recordings and behavioral approaches. These interneurons present a typical synchronized pause in their tonic activity in response to salient stimuli during reinforcement learning, pause which can be preceded or followed by bursts. We are exploring whether and how this complex pattern impacts long-term plasticity at the glutamate synapses established by the cortical inputs onto the striatal projection neurons, one main presumed cellular substrate of striatum-related learning. Iterative interactions between experiments and modeling will greatly increase our understanding of such complex operations. Computational models benchmarked based on the experimental data to be collected would be essential to dissect out the response parameters pivotal for corticostriatal long-term plasticity and its control by cholinergic interneurons. They would not only help interpreting physiological data but also predict the effect of manipulating particular components of the circuit, at cellular, network and behavioral levels, providing a test-bed for enriching the architectural and functional hypotheses prior to in vivo testing.

Our team has also long lasting interest in studying glutamate-mediated neurotransmission and the cytotoxic consequences of dysfunction at glutamate synapses, focusing on glutamate transporters. In particular, we previously provided evidence that dopamine neurons in the substantia nigra pars compacta, whose neurodegeneration is a pathological hallmark of Parkinson’s disease, show a preferential vulnerability to dysfunction of glutamate transporters.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/biology-of-ciliated-epithelia/

Team leader : Laurent Kodjabachian

Research domain : Cell and developmental biology

Contact : Laurent Kodjabachian - laurent.kodjabachian@univ-amu.fr

Ciliated epithelia harbor numerous cilia that beat in a coordinated and directional manner to propel biological fluids. They are used for locomotion by small invertebrate animals, and help airway cleaning, cerebrospinal fluid circulation in the brain, and egg transportation in the oviduct in mammals. Ciliated epithelia represent fascinating tissues to study cell fate determination, epithelial morphogenesis and regeneration, centriole and cilia biology, cell and tissue polarity, or hydrodynamics. We currently focus our attention on the mechanisms that determine the number of ciliated cells and their spatial distribution in the epithelium, and at a smaller scale those that control the number of cilia and their orientation.

We study those problems in the embryo of the amphibian Xenopus and the post-natal mouse brain, as well as in cultured ciliated cells. We strive to implement live imaging, super-resolution microscopy and genome editing in our models.

We would like to capture some of the processes we study in mathematical equations, so as to help us building up the most plausible scenarios. To reach this objective, we work hard on systematically quantifying as many biological parameters as possible.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/morphogenesis-and-cell-compartimentation/

Team leader : André Le Bivic

Research domain : Cell biology

Contact : André Le Bivic - andre.le-bivic@univ-amu.fr

Our group aims at understanding how a specialized layer of cells called epithelium has appeared during evolution to allow the development of our branch of living species ie the animals (metazoans). This was made possible with the invention of a set of proteins that promote cell-cell adhesion (E-cadherins) and the definition of the polarity axis around the adhesive structures (the polarity complexes). We want to understand at the molecular, cellular and tissue levels how these proteins interact to build a hierarchical model and to try to identify their primitive functions essential to build the first epithelial layer. In particular, how the interactions between all these protein complexes allow specific morphologies and behavior of epithelial cells by controlling a network of mechanical forces.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/cell-polarity-and-tissue-morphogenesis/

Team leader : Thomas Lecuit

Research domain : Development biology, morphogenesis, signaling, in vivo imaging

Contact : Thomas Lecuit - thomas.lecuit@univ-amu.fr

Epithelia form mechanical and chemical barriers that are both structurally robust and constantly remodelled during embryogenesis and organogenesis from nematodes to humans. Perturbations in this balance underlie solid cancer progression. How this is controlled is a fundamental unanswered question in biology. Our major ambition is to understand this problem using interdisciplinary approaches that combine the most quantitative analyses with physiological studies in whole organisms.  We decipher the biochemical underpinnings of cell and tissue mechanics, namely how forces are generated and how they produce deformations, and characterize their regulation by conserved signalling pathways. Our group requires the complementary expertise of cell and developmental biologists, physicists and engineers etc.

One of the most remarkable properties of living tissues is that they combine robustness in their organisation, and extensive plasticity in their dynamics. This is especially true in epithelial sheets, where cells are usually (but not always) arranged in monolayers. Through the tight association between cells mediated by adhesion molecules, in particular E-cadherin, cells are cohesive and allow the formation of epithelial barriers that separate different physiological environments and protect the organism against pathogens. Epithelia also extensively remodel during development, and in the adult. For instance, epithelia grow and produce new cells via cell division. Cells remodel their contacts and move with respect to each other and contribute to the remodelling of the tissue.

Through these remodelling events, tissues acquire complex shapes and maintain their final organization as new cells replace dead cells.

Tissue robustness requires adhesion mediated by E-cadherin complexes. Plasticity is an active process driven by actomyosin contractility whereby cells remodel their contacts. These forces are transmitted at the cell contacts by E-cadherin complexes.

We address the following major questions:

• how forces emerge from interactions between motors, actin filaments and crosslinker.
• How E-cadherin complexes control adhesion and force transmission.
• How intercellular developmental signals control cell mechanics to drive tissue extension and invagination.
• How cell division and tissue growth affect tissue mechanics and vice versa.

We use the fruitfly Drosophila to address these problems. The major components of cell mechanics and their regulation are shared with humans and this organism lends itself to a very powerful combination of functional, molecular and physical approaches. Our group is largely interdisciplinary and employs a large battery of experimental methods ranging from biochemistry, to genetics, quantitative imaging and modelling.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/physical-approaches-to-cell-dynamics/

Team leader : Pierre-François Lenne

Research domain : Physics of living systems, imaging, morphogenesis

Contact : Pierre-François Lenne - pierre-francois.lenne@univ-amu.fr

We are interested in understanding the physical principles that underpin the morphogenesis of animals. How do cells self-organize, move and change shape to give rise to multicellular organisms,?

To tackle these questions, we study how cells interact during morphogenesis.  In particular, we study the forces and the organization of supramolecular components that shape cell-cell contacts and tissues. We try also to understand how biochemical signaling and mechanics interact to organize spatially cell ensembles.

We integrate both physics (imaging/mechanics/modelling) and experimental biology to investigate morphogenetic processes in different model systems: the fruit fly, a small worm called C. elegans, and more recently, aggregates of embryonic stem cells.

We believe that we can propose a set of conceptual and experimental approaches to study living systems.  We have some experience in designing and developing experiments to measure quantitative parameters, such as forces and molecular interactions, which are important to understand living systems. Our group also develops theoretical models to make quantitative and falsifiable predictions, which we test experimentally. Modeling is also a guide for new experiments.  Our projects require input from physics and biology, and we are facing challenges in analysing cell behaviours, which would greatly benefit from a mathematical input.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/axon-guidance-in-the-mammalian-brain/

Team leader : Fanny Mann

Research domain : Cell and molecular biology, biochemistry

Contact : Fanny Mann - fanny.mann@univ-amu.fr

Our team is studying how neurons wire together during the development of the nervous system and how neuronal circuits are reorganized in organs affected by cancer.

Normal brain function depends on complex patterns of neuronal circuits that develop during fetal life and childhood. Several neurological disorders result from alterations that occur during the construction of brain networks.

Neurons connect to each others by extending long cables, called axons, whose growth is not random but precisely oriented towards their targets by axon guidance molecules. Our team studies the mechanisms that contribute to the fine regulation of guidance cue activities to ensure the accuracy and fidelity of axonal trajectories.

In addition to being essential to brain development, axon guidance molecules are also present in adult organisms where their expression can be reactivated under pathological conditions such as cancer. We are investigating whether their activity could contribute to the innervation of malignant tumors, a process that is still poorly characterized but can influence the course of the disease.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/neural-stem-cell-plasticity/

Team leader : Cédric Maurange

Research domain : Cell biology, neurosciences

Contact : Cédric Maurange - cedric.maurange@univ-amu.fr

We are interested in the mechanisms that regulate neural stem cell self-renewal and differentiation both during development and tumorigenesis. For this purpose, we are investigating the gene regulatory networks involved in these process and the extrinsic or cell-intrinsic signals that promote the bistable switch between self-renewal and differentiation. We are using the fruitfly Drosophila as a simple model organism that allows the use of unmatched genetic tools and the dissection of basic principles conserved in higher animals such as mammals.

In addition to the usual genetic and molecular biology tools, we would like to use the power of computer/mathematical modelling in order to rationalise our approach to specific problems.

• One way would be through the modelling of genetic networks involving different sorts of feedback loops
• Another problem we are currently particularly interested in is to decipher the rules of cellular hierarchy within tumors, a long-standing question in the cancer field.

The concept of cellular hierarchy in cancers implies that tumors are organized in a manner that is similar to tissues, with a stem cell at the top the cellular hierarchy. In tissues, stem cells give rise to intermediate progenitors that have a limited proliferation potential and rapidly differentiate in matured cells. In tumors, cancer stem cells (CSCs) may also self-renew and give rise to intermediate progenitors. However, while the balance between stem cell self-renewal and differentiation is well controlled in developing tissues allowing limited tissue growth, this balance is perturbed in tumors allowing CSCs to propagate unlimited tumor growth through unlimited self-renewal. In many cancers, we still don’t understand what dictate the choice between self-renewal and differentiation, and if we could understand this, we could design strategies to force differentiation at the expense of self-renewal, and eliminate CSCs to cure cancer.

We have established a Drosophila tumor model that contains both CSC-like cells and intermediate progenitors. We would like to collaborate with mathematicians/biophysicists to generate a computer model that may help us to understand how the choice to self-renew or differentiate is regulated in such tumors, and test predictions using the power of Drosophila genetics.

The modeling will be designed following some initial constraints that are based on some observations we have made in Drosophila neural tumors - for example:

• the 2D-3D organization of CSCs (they are organized in clusters),
• the proportion of CSCs in the tumor (constant),
• the different cell types with limited self-renewing potential they can give rise.

The models and simulations will aim to help answering the following questions:

1. Is the spatial organization of the CSCs important for the regulation of the CSC population? Is the decision to self-renew or differentiate depending on the position of the CSC within the clusters and the type of contacts with the neighboring cells? What drives cluster dissemination within the tumor?
2. What are the parameters that fix the proportion of CSCs?
3. Which changes in parameters could explain the different CSC proportions and cluster size observed in various genetic contexts?

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/physical-and-molecular-principles-governing-cytoskeletal-organization/

Team leader : Alphée Michelot

Research domain : Biophysics, biochemistry, genetics and cell biology

Contact : Alphée Michelot - alphee.michelot@univ-amu.fr

Our team is working on the actin cytoskeleton, which is a network of biological polymers present in all eukaryotic cells. Cells control the dynamic assembly and disassembly of these networks, and use them as a force-generating machinery in a wide diversity of cellular processes.

We have three main objectives. Our first aim is to understand some of the basic physical and biochemical principles governing actin organization. Our second aim is to understand how cells modulate the mechanical properties of these networks thanks to a battery of molecular regulators. Our last aim is to understand how perturbations brought to the actin cytoskeleton affect various cellular functions.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/specification-of-heterogeneity-in-somatic-sensory-neurons/

Team leader : Aziz Moqrich

Research domain : Pain biology

Contact : Aziz Moqrich - aziz.moqrich@univ-amu.fr

Pain is commonly classified into acute and chronic. Acute pain arising from tissue injury is short lasting and is essential for the maintenance of our physical integrity. In contrast, chronic pain persists beyond the normal time of tissue healing and adversely impacts on our well-being. While we know a great deal about the mechanisms underlying the onset of acute pain, our knowledge on the molecular and cellular mechanisms that trigger the transition from acute to chronic pain is extremely sketchy. In the last years the Moqrich group has made two major discoveries:

1- We identified an unconventional myosin protein whose Loss-of-Function (LoF) converts a short lasting acute and reversible inflammatory, neuropathic and postoperative pain into a long lasting and irreversible chronic pain.

2- We uncovered a chemokine-like protein TAFA4 endowed with a strong analgesic effect against inflammatory and neuropathic pain conditions (Delfini et al., 2013). Therefore, using this unique mouse model in combination with state-of-the-art RNA seq and proteomics and behavioral pharmacology will allow us (i) deciphering the molecular and cellular mechanisms underlying the transition from acute to chronic pain and (ii) designing efficient preventive/curative therapeutic strategies for chronic pain.

This project fits perfectly well with the philosophy of the CenTuri project as it will require strong expertise in mouse genetics, molecular and cellular biology and Bioinformatics. A close collaboration between my group and the group of Bianca HABERMANN is already established. We believe that this close collaboration will be instrumental and will allow extending the understanding of the molecular mechanisms underlying the transition from acute to chronic pain. For example: given that chronic pain has different etiologies, we will address whether (i) chronic pain provoked by an inflammatory agent activates the same genetic programs as those leading to chronic pain after nerve injury or post-surgery, (ii) we will decipher whether inflammation-induced chronic pain markers are the same as those expressed under nerve injury or after surgery, (iii) we will also address how much contribution of the molecular changes occurring in dorsal root ganglia neurons versus those occurring in the spinal cord account for the development of chronic pain.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/immune-response-and-development-in-drosophila/

Team leader : Julien Royet

Research domain : Immunity, behavior, signalling

Contact : Julien Royet - julien.royet@univ-mrs.fr

We used Drosophila to decipher the interactions between the bacteria and its host. Our recent data suggest that in addition to trigger an immune response, infectious bacteria can modulate the behaviour of the host. We would like to identify the molecules and mechanisms that mediate the dialog between the bacteria either infectious or commensal (in the gut) and an eukaryote host.

As a teacher and future head of the Integrative Biology and Physiology Master, I am very interest to establish close contact with the person who will teach in the future CenTuri associated Master and probably to set up course that will be share by the two Masters.

As a researcher, our team is working at the intersection between microbiology, genetics, immunology and neurosciences and is therefore very into integrative research.

Campus / location : Luminy

Website : http://www.ibdm.univ-mrs.fr/equipe/muscle-dynamics/

Team leader : Frank Schnorrer

Research domain : Developmental and cell biology

Contact : Frank Schnorrer - frank.schnorrer@univ-amu.fr

We are developmental biologists that study how muscles are built.

We are particularly interested in how the molecular machines called sarcomeres, which produce the contractile forces of muscles, are built during muscle development.

We use Drosophila as our model and combine live in vivo imaging with genetics and laser micro-manipulations. We are quantifying forces at a tissue level and recently also at a molecular level to understand how forces participate in the assembly of the contractile structures.

We found that sarcomeres assemble simultaneously into long linear chains called myofibrils. We favour a force driven self-assembly mechanisms of the individual molecular components into periodic contractile units. It is important that each of this long periodic myofibrils is anchored at both of its ends in order to able to apply force. If anchoring is blocked, assembly of periodic myofibrils fails.