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Associated laboratories : Collège de France

Center for Interdisciplinary Research in Biology – CIRB


Chromosome dynamics

Chromosomes are gigantic molecules that are compacted in a robust but plastic and dynamic structure that allows gene expression and cell cycle related deformations. In bacteria, chromosome organization is a mosaic of structuring elements, including topological structures, transcription clusters, histone like scaffolds and mega bases large macrodomains. In response to cytoplasmic or environmental stimuli the network formed by these elements will adapt to allow the adequate cell response. Our project proposes to characterize the molecular bases of this network. Thanks to state of the art molecular biology and cell biology techniques we will address the relationships between DNA conformation and gene expression at reporter loci or at the whole genome scale.
Contact : Olivier Espeli

Neural Circuits and Behavior

Our laboratory is interested in the functional properties of neural circuits underlying olfactory sensory processing. We use an interdisciplinary approach, combining molecular mouse genetics, in vivo brain imaging and behavioral experiments to understand the logic of odor coding in higher olfactory centers in the cortex.
Two-photon in vivo imaging and behavioral analyses of transgenic mice with a ’monoclonal nose’ (Fleischmann et al., 2008) have suggested a model of olfactory processing in which the recognition of patterns of neural activity, or contrast, is critical for odor detection. To test this model, we exploit a set of genetic perturbations in transgenic mice, which alters the expression of odorant receptor genes. We use state-of-the-art in vivo imaging approaches to reveal how genetically defined patterns of glomerular activity are transformed into higher order odor representations in the cortex, and we examine the consequences of such perturbations in assays for innate and learned olfactory-driven behaviors.
Contact : Alexander Fleischmann

Formation and Evolution of Skin Patterns in the Zebra Finch

Understanding how populations diversify is a fundamental goal in biology. Since most major morphological traits are established during embryogenesis, deciphering how developmental processes produce trait variation is key to understanding biodiversity. Our laboratory uses skin pattern (i.e., the distribution of color and dermal appendages across the body) as a model system, a trait crucial for survival and reproductive success that varies tremendously in nature.
Simple color patterning involves the establishment of embryonic pre-patterns characterized by the spatial restriction of pigmentation genes. However, how pre-patterns form and evolve has remained a black box. The goal of this research project is to (1) dissect the developmental events that establish discrete domains in the skin, and (2) decipher how changes in these mechanisms contribute to natural variation in this trait. We will address this question by using the zebra finch (genus Taeniopygia), a songbird displaying a simple color pattern, because it is amenable to in ovo micro-manipulation, genetics, and molecular biology. We will conduct lineage experiments followed by analyses of gene expression and functional validation to investigate the embryonic origin and the molecular nature of the signals providing positional information in the skin
Contact : Marie Manceau

Neuroglial Interactions in Cerebral Physiopathology

The main goal of our group is to determine whether and how astrocytes play an active and direct role in information processing. We want to unravel the molecular modalities and functional outcomes of neuroglial interactions in physiological and pathological conditions. More precisely, we want to understand how neurons and glia communicate in various regimes of activity and determine the outcome of disrupting their communication on neuronal functions, including their excitability, synaptic transmission, plasticity and synchronization. To overcome the present conceptual and experimental difficulties in the field of neuroglial interactions, we have developed a challenging novel interdisciplinary approach combining electrophysiology, imaging, molecular biology, biochemistry, mathematical modeling and new pharmacological strategies and molecular tools targeted to astrocytes, which permit to analyze and act selectively on populations of astrocytes. Indeed, a particularly original aspect of our research in this field consists in using tools targeting specifically astrocytes : either pharmacological tools, delivered intracellularly in single astrocytes through a patch pipette and then diffusing in the gap-junction mediated network, molecular tools, such as knockout mice for astrocytic proteins, novel engineered lentiviral vectors targeting specifically astrocytes or mathematical simulation tools. Using this multidisciplinary and innovative strategy, our goal is to decipher the specific role of key astroglial properties, such as calcium signalling, membrane ionic currents, as well as connexin and pannexin-mediated transmission in basal synaptic activity, synaptic plasticity, synchronous physiological and pathological network activities in situ and in vivo.
Contact : Nathalie Rouach

Mice, Molecules and Synapse Formation

Our team’s goal is to provide new insights on the formation of functional neural networks in vivo, in particular through identification of the genes and proteins controlling synapse specificity.
We have developed the synapse protein profiling approach, which enables the purification of a specific type of synapse from the mouse brain and identification of its protein content.
We are performing the first comparison of the protein content of two types of excitatory synapses made on the same neuronal target, to identify the proteins characterizing the “molecular synaptic code”. Selected synapse specific signalling pathways are studied in depth to identify their function during brain development and their contribution to brain diseases using a combination of genetic, biochemical and imaging approaches both in culture systems and in the mouse brain. Using this strategy, we have recently identified the role of the adhesion-G protein coupled receptor BAI3, a gene associated with psychiatric disorders, in the coordination of dendritogenesis and synaptogenesis during brain development.
Contact : Fekrije Selimi

Intercellular Communication and Microbial Infections

Our team is interested in the mechanisms allowing pathogenic bacteria to subvert host cell functions.
Pathogenic bacteria express virulence determinants that enable them to colonize and invade host cell tissue.
These determinants could be surface proteins that act as “adhesins” or “invasins” that target host cell receptors, thereby providing the mechanical bacterial link to the cell surface. Other virulence determinants can be secreted in the extracellular medium and acting as pore, or by penetrating into host cells, can affect the integrity of an epithelial barrier.
The team’s research is focused on the characterization of the function of virulence determinants and signalling pathways involved in bacterial-induced cytoskeletal reorganization or controlling cell death, using Shigella, enteropathogenic Esherichia coli (EPEC) and Streptococcus pneumoniae (pneumoococcus) as bacterial models. To gain insights into the functional coordination of these effectors during bacterial infection, we are developing a combination of genetic, cellular, molecular and imaging techniques in order to characterize dynamic aspects of bacterial cell interactions. The team actively collaborates with structural biologists, biophysicists, and mathematicians to study original aspects concerning the function of bacterial effectors, intercellular communication, as well as mechanical constraints during bacterial-host cell interaction.
Contact : Guy Tran-van-Nhieu

Asymmetric Divisions in Oocytes

Asymmetric division is a widespread mechanism promoting cell diversity. Oocytes from higher eukaryotes undergo asymmetric divisions in size, leading to the formation of a large cell, the oocyte and two small ones, the polar bodies. This allows most of the maternal stores to be retained in the oocyte, a vital condition for further embryo development. We study meiotic spindle morphogenesis and positioning, key events ensuring the asymmetry of meiotic divisions in oocytes. In somatic cells, the spindle axis is determined by the position of the two opposing centrosomes before entry into mitosis. In these cells, movement and orientation of the spindle are in close relationship with the polarity axis of the mother cell, and occurs via astral microtubules emanating from the centrosomes located at spindle poles. However, prophase oocytes do not have a pre-defined polarity, and meiotic spindles organize in the absence of canonical centrosomes, thus in absence of their associated astral microtubules. We currently investigate how meiotic spindles are assembled and positioned in the absence of canonical centrosomes and how this can impact on the oocyte ploidy.
Contact : Marie-Hélène Verlhac

Regeneration and morphogenesis in Zebrafish

One major issue in regenerative medicine is the choice between an imperfect wound repair and a faithful regeneration. Our laboratory explores the function of early signals induced by lesion during the process of fin regeneration. Indeed Zebrafish provides relevant models to investigate this question as it can regenerate most of its organs and complete appendages at adulthood. We recently showed that oxidative stress and purine signalling are involved in cell plasticity and we used optogenetic tools to manipulate these signals in vivo in order to decipher the hierarchy of signalling cascade in tissue remodelling and regeneration.
Contact : Sophie Vriz

Stochastic models for the inference of life evolution (SMILE)

Probabilistic models of evolution can be used to infer the historical patterns of species diversification from the knowledge of genotypes and phenotypes of contemporary species : identification of source regions of biodiversity in geographical space or in niche space, reconstruction of traits of ancestral species, inference of diversification rate shifts across paleontological time, etc.
The SMILE group gathers mathematicians, biologists and computer scientists to investigate and understand the process of species diversification, using three different approaches :

  1. A lineage-based approach enabling the inference of diversification processes from phylogenies ;
  2. An individual-based approach based on the modeling of either population genetics or ecological interactions in the speciation process, or both ;
  3. Mathematical studies linking the former approach to the latter one by means of limit theorems (separation of timescales, invariance principles, dimension reduction, etc.).

Contact : Amaury Lambert