The translation apparatus has long been viewed as a mere factory until recent findings this last decade have unraveled its unexpected role in orchestrating real time gene regulation. Far from being a molecular monolith, the ribosome displays a remarkable heterogeneity along with a striking ability to orchestrate real-time control of gene expression. In the meantime, several reports connect alteration of the translation machinery with elevated cancer risk as well as in tumor initiation and progression. We aim to decipher the variety of translation mechanisms by modeling dedicated Ribo-sequencing experiments. We have designed a new set of Ribo-seq experiments with purified polysomes in order to understand the role of the ribosome density onto translation and to characterized biophysical parameters of translations (hopping rates of ribosomes, initiation rate, termination rate). Preliminary data will be modeled as a proof of concept to pave the way to a genome wide analysis with morefinely regulated genes in charge, e.g., for cell phenotype. After a presentation of the physical perspective of translation, I will discuss the usefulness of biophysical modeling approaches to estimate the codon-dependent hopping, initiation and termination rates of ribosomes from Ribo-seq data. I will discuss designed Ribo-seq experiments (purified polysomes) obtained at IGF suggesting that the ribosome dynamics depends on various conditions: modified dynamics of the first ribosome entering the newly transcripted mRNA, different paradigms for translation (cytoplasmic versus membrane translation), effect of inhomogeneous hopping rates on ribosome traffic etc. Finally, I will consider how these findings will help to understand the epithelial-mesenchymal transition: we have performed designed Ribo-seq experiments inducing a change of the ribosomes concentration level in vivo in tumor human cells and observed induced change of phenotype to mezenchymal cells.

Controlled motion and positioning of colloids and macromolecular complexes in a fluid, as well ascatalytic particles in active environments, are fundamental processes in physics, chemistry andbiology. Here we focus on an active biological system for which precise experimental results areavailable. Our work is fully inspired by studies of one of the most widespread and ancientmechanisms of liquid phase macromolecular segregation and positioning known in nature:bacterial DNA segregation systems. Efficient bacterial chromosome segregation typically requiresthe coordinated action of a three-component, fueled by adenosine triphosphate machinery calledthe partition complex. We can distinguish two steps: (i) a process of phase transition [2,3] tobuilt a membraneless region of high protein concentration (partition complex) (ii) the action ofmolecular motor action upon the complex to create a chemical force.We present a phenomenological model [1] accounting for the dynamics of this system that is alsorelevant for the physics of catalytic particles in active environments. The model is obtained bycoupling simple linear reaction-diffusion equations with a volumetric chemophoresis force fieldthat arises from protein-protein interactions and provides a physically viable mechanism forcomplex translocation. This description captures experimental observations: dynamic oscillationsof complex components, complex separation and symmetrical positioning. The predictions of ourmodel are in agreement with and provide substantial insight into recent experiments. From a non-linear physics view point, this system explores the active separation of matter at micrometricscales with a dynamical instability between static positioning and travelling wave regimestriggered by the dynamical spontaneous breaking of rotational symmetry. We also discuss thephase transition mechanism giving rise to macromolecular assembly of proteins. Our predictionsare compared to Super Resolution microscopy and microbiology experiments [1,2,3].[1] Walter J.-C., Dorignac J., Lorman V., Rech J., Bouet J.-Y., Nollmann M., Palmeri J., ParmeggianiA. and Geniet F., Phys. Rev. Lett. 119, 028101 (2017).[2] Debaugny R., Sanchez A., Rech J., Labourdette D., Dorignac J., Geniet F., Palmeri J.,Parmeggiani A., Boudsocq, Leberre V., Walter* J.-C. and Bouet* J.-Y Mol. Syst. Biol. 14, e8516 (2018).[3] David G., Walter J.-C., Broedersz C., Dorignac J., Geniet F., Parmeggiani A., Walliser N.-O. andPalmeri J., submitted to Phys. Rev. Lett. [arXiv/1811.09234] (2019).

Controlled motion and positioning of colloids and macromolecular complexes in a fluid, as well as catalytic particles in active environments, are fundamental processes in physics, chemistry and biology. Here we focus on an active biological system for which precise experimental results are available. Our work is fully inspired by studies of one of the most widespread and ancient mechanisms of liquid phase macromolecular segregation and positioning known in nature: bacterial DNA segregation systems. Efficient bacterial chromosome segregation typically requires the coordinated action of a three-component, fueled by adenosine triphosphate machinery called the partition complex. We can distinguish two steps: (i) a process of phase transition [2,3] to built a membraneless region of high protein concentration (partition complex) (ii) the action of molecular motor action upon the complex to create a chemical force. We mainly present a phenomenological model of reaction-diffusion for two families of proteins [1] describing the step (ii), the dynamics of the segregation of paired chromosomes. We also discuss the step (i) the phase transition mechanism giving rise to macromolecular assembly of proteins. Our predictions are compared to Super Resolution microscopy and microbiology experiments [1,2,3].[1] Walter J.-C., Dorignac J., Lorman V., Rech J., Bouet J.-Y., Nollmann M., Palmeri J., Parmeggiani A. and Geniet F., Phys. Rev. Lett. 119, 028101 (2017).[2] Debaugny R., Sanchez A., Rech J., Labourdette D., Dorignac J., Geniet F., Palmeri J., Parmeggiani A., Boudsocq, Leberre V., Walter* J.-C. and Bouet* J.-Y Mol. Syst. Biol. 14, e8516 (2018)[3] David G., Walter J.-C., Broedersz C., Dorignac J., Geniet F., Parmeggiani A., Walliser N.-O. and Palmeri J., submitted to Phys. Rev. Lett. [arXiv/1811.09234] (2019).

Controlled motion and positioning of colloids and macromolecular complexes in a fluid, as well as catalytic particles in active environments, are fundamental processes in physics, chemistry and biology. Here we focus on an active biological system for which precise experimental results are available. Our work is fully inspired by studies of one of the most widespread and ancient mechanisms of liquid phase macromolecular segregation and positioning known in nature: bacterial DNA segregation systems. Efficient bacterial chromosome segregation typically requires the coordinated action of a three-component, fueled by adenosine triphosphate machinery called the partition complex. We can distinguish two steps: (i) a process of phase transition [2,3] to built a membraneless region of high protein concentration (partition complex) (ii) the action of molecular motor action upon the complex to create a chemical force. We present a phenomenological model [1] accounting for the dynamics of this system that is also relevant for the physics of catalytic particles in active environments. The model is obtained by coupling simple linear reaction-diffusion equations with a volumetric chemophoresis force field that arises from protein-protein interactions and provides a physically viable mechanism for complex translocation. This description captures experimental observations: dynamic oscillations of complex components, complex separation and symmetrical positioning. The predictions of our model are in agreement with and provide substantial insight into recent experiments. From a non-linear physics view point, this system explores the active separation of matter at micrometric scales with a dynamical instability between static positioning and travelling wave regimes triggered by the dynamical spontaneous breaking of rotational symmetry. We also discuss the phase transition mechanism giving rise to macromolecular assembly of proteins. Our predictions are compared to Super Resolution microscopy and microbiology experiments [1,2,3].[1] Walter J.-C., Dorignac J., Lorman V., Rech J., Bouet J.-Y., Nollmann M., Palmeri J., Parmeggiani A. and Geniet F., Phys. Rev. Lett. 119, 028101 (2017).[2] Debaugny R., Sanchez A., Rech J., Labourdette D., Dorignac J., Geniet F., Palmeri J., Parmeggiani A., Boudsocq, Leberre V., Walter* J.-C. and Bouet* J.-Y Mol. Syst. Biol. 14, e8516 (2018)[3] David G., Walter J.-C., Broedersz C., Dorignac J., Geniet F., Parmeggiani A., Walliser N.-O. and Palmeri J., submitted to Phys. Rev. Lett. [arXiv/1811.09234] (2019).

W propose biophysical approach to offer a mechanistic view of translational. The goal is to be able to use Ribo-sequencing data to estimate biophysical parameters of translation like: initiation, elongation and termination rates in order to make prediction on the cancerous cell phenotype.

Efficient bacterial chromosome segregation typically requires the coordinated action of a three-component, fueled by adenosine triphosphate machinery called the partition complex. We present a phenomenological model accounting for the dynamic activity of this system that is also relevant for the physics of catalytic particles in active environments. The model is obtained by coupling simple linear reaction-diffusion equations with a proteophoresis, or “volumetric” chemophoresis, force field that arises from protein-protein interactions and provides a physically viable mechanism for complex translocation. This minimal description captures most known experimental observations: dynamic oscillations of complex components, complex separation and subsequent symmetrical positioning. The predictions of our model are in phenomenological agreement with and provide substantial insight into recent experiments. From a non-linear physics view point, this system explores the active separation of matter at micrometric scales with a dynamical instability between static positioning and travelling wave regimes triggered by the dynamical spontaneous breaking of rotational symmetry.

The DNA shows a high degree of spatial and dynamical organization over a broad range of length scales. It interacts with different populations of proteins and can form protein-DNA complexes that underlie various biological processes, including chromosome segregation. A prominent example is the large ParB-DNA complex, an essential component of a widely spread mechanism for DNA segregation in bacteria. Recent studies suggest that DNA-bound ParB proteins interact with each other and condense into large clusters with multiple extruding DNA-loops. In my talk, I present the Looping and Clustering model [1], a simple statistical physics approach to describe how proteins assemble into a protein-DNA cluster with multiple loops. Our analytic model predicts binding profiles of ParB proteins in good agreement with data from high precision ChIP-sequencing – a biochemical technique to analyze the interaction between DNA and proteins at the level of the genome. The Looping and Clustering framework provides a quantitative tool that could be exploited to interpret further experimental results of ParB-like protein complexes and gain some new insights into the organization of DNA.[1] Walter, J.-C., Walliser, N.-O., ... & Broedersz, C. P., New J. Phys. 20, 035002 (2018).