Section: Partnerships and Cooperations

National Initiatives

ANR RNAGRIMP

Participants : Florence Besse [PI] , Fabienne de Graeve, Xavier Descombes, Eric Debreuve, Somia Rahmoun.

Here, we propose to study the molecular bases underlying the assembly and regulation of RNA granules, using the highly conserved IMP-containing granules as a paradigm. Specifically, we propose to perform an unbiased genome-wide RNAi screen on Drosophila cultured cells to identify mutant conditions in which the organization and/or distribution of IMP-containing granules is altered. To quantitatively and statistically analyze mutant conditions, and to define precise and coherent classes of mutants, we will combine high throughput microscopy with the development of a computational pipeline optimized for automatic analysis and classification of images. The function of positive hits isolated in the screen will then be validated in vivo in Drosophila neurons using fly genetics and imaging techniques, and characterized at the molecular and cellular levels using biochemical assays, in vitro phase transition experiments and live-imaging. Finally, the functional conservation of identified regulators will be tested in zebrafish embryos combining gene inactivation and live-imaging techniques. This integrative study will provide the first comprehensive analysis of the functional network that regulates the properties of the conserved IMP RNA granules. Our characterization of the identified regulators in vivo in neuronal cells will be of particular significance in the light of recent evidence linking the progression of several degenerative human diseases to the accumulation of non-functional RNA/protein aggregates.

This 4-years project started january, 2016 and is leaded by F. Besse (iBV, Nice). Participants are iBV, institut de biologie Paris Seine (IBPS, Paris), and Morpheme.

ANR HMOVE

Participants : Xavier Descombes, Eric Debreuve, Somia Rahmoun.

Among the signaling molecules involved in animal morphogenesis are the Hedgehog (Hh) family proteins which act at distance to direct cell fate decisions in invertebrate and vertebrate tissues. To study the underlying process we will develop accurate tracking algorithm to compare trajectories of different Hh pools transportation in live animals. This will allow us to analyze the contribution of the different carriers in the establishment of the Hh gradient. Moreover, we will develop new methods to modify the spatio-temporal and dynamical properties of the extra-cellular Hh gradient and separate the contribution of the apical versus basal Hh pools. We will complete this study with a genome-wide screen to identify genes and related cellular processes responsible for Hh release. The particular interest of this collaboration lies in the combination of development of tracking algorithm to analyze Hh distribution and trajectories with extremely powerful genetics, ease of in vivo manipulation and lack of genetic redundancy of Drosophila.

This 4-years project started january, 2016 and is leaded by P. Thérond (iBV, Nice). Participants are iBV and Morpheme.

ANR Cell Whisper

Participant : Grégoire Malandain.

Successful embryogenesis requires the differentiation of the correct cell types, in defined numbers and in appropriate positions. In most cases, decisions taken by individual cells are instructed by signals emitted by their neighbours. A surprisingly small set of signalling pathways is used for this purpose. The FGF/Ras/ERK pathway is one of these and mutations in some of its individual components cause a class of human developmental syndromes, the RASopathies. Our current knowledge of this pathway is, however, mostly static. We lack an integrated understanding of its spatio-temporal dynamics and we can imperfectly explain its highly non-linear response to a graded increase in input stimulus.

This systems biology project combines advanced quantitative live imaging, pharmacological/optogenetics perturbations and computational modelling to address 3 major unanswered questions, each corresponding to a specific aim:

• Aim 1: What is the spatio-temporal dynamic of intracellular signal transduction in response to FGF?

• Aim 2: What is the molecular basis of the switch-like response to graded extracellular signals?

• Aim 3: Can the results be integrated into a predictive computational model of the pathway?

Through this approach, in a simplified model system, we hope to gain an integrated view of the pathway’s dynamics.

This 4-years project started october the 1st, 2019 and is leaded by P. Lemaire (CRBM, Montpellier). Participants are CRBM (Montpellier), LIRMM (Montpellier), MOSAIC (Inria Grenoble) and Morpheme.

Inria Large-scale initiative Naviscope

Participant : Grégoire Malandain.

This action gathers the expertise of seven Inria research teams (Aviz, Beagle, Hybrid, Morpheme, Parietal, Serpico and Mosaic) and other groups (MaIAGE, INRA, Jouy-en-Josas and UMR 144, Institut Curie Paris) and aimed at developing original and cutting-edge visualization and navigation methods to assist scientists, enabling semi-automatic analysis, manipulation, and investigation of temporal series of multi-valued volumetric images, with a strong focus on live cell imaging and microscopy application domains. More precisely, the three following challenges will be addressed:

• Novel machine learning methods able to detect the main regions of interest, and automatic quantification of sparse sets of molecular interactions and cell processes during navigation to save memory and computational resources.

• Novel visualization methods able to encode 3D motion/deformation vectors and dynamics features with color/texture-based and non-sub-resolved representations, abstractions, and discretization, as used to show 2D motion and deformation vectors and patterns.

• Effective machine learning-driven navigation and interaction techniques for complex functional 3D+Time data enabling the analysis of sparse sets of localized intra-cellular events and cell processes (migration, division, etc.).