Gene expression consists in the synthesis of proteins from the information encoded on DNA. One of the two main steps of gene expression is the translation of messenger RNA (mRNA) into polypeptide sequences of amino acids. Here, by taking into account mRNA degradation, we model the motion of ribosomes along mRNA with a ballistic model where particles advance along a filament without excluded volume interactions. Unidirectional models of transport have previously been used to fit the average density of ribosomes obtained by the experimental ribosome sequencing (Ribo-Seq) technique. In this case an inverse fit gives access to the kinetic rates: the position-dependent speeds and the entry rate of ribosomes into mRNA. The degradation rate is not, however, accounted for and experimental data from differentexperiments are needed to have enough parameters for the fit. Here, we propose an entirely novel experimental setup and theoretical framework consisting in splitting the mRNAs into categories depending on the number of ribosomes from one to four. We analytically solve the ballistic model for a fixed number of ribosomes per mRNA, study the different regimes of degradation, and propose a criterion for the quality of the inverse fit. The proposed method provides a high sensitivity to the mRNA degradation rate. The additional equations coming from using the monosome (single ribosome) and polysome (arbitrary number) Ribo-Seq profiles enables us to determine all the kinetic rates in terms of the experimentally accessible mRNA degradation rate.

For small tension the response of a solid to an applied stress is given by Hooke’s law. Outside this linear regime the relation between stress and strain is no longer universal and at present there is no satisfactory insight on how to connect for disordered materials the stress-strain relation to the microscopic properties of the system. Here we use atomistic computer simulations to establish this connection for the case of silicate glasses containing alkali modifiers. By probing how in the highly non-linear regime the stress-strain curve depends on composition, we are able to identify the microscopic mechanisms that are responsible for the complex dependence of stress on strain in these systems, notably the presence of an unexpected quasi-plateau in the tangent modulus. We trace back this dependence to the mobility of the modifiers which, without leaving their cage or modifying the topology of the network, are able to relieve the local stresses. Since the identified mechanism is general, the results obtained in this study will also be helpful for understanding the mechanical response of other disordered materials.

Polycomb (Pc) group proteins are transcriptional regulators with key roles in development, cell identity and differentiation. Pc-bound chromatin regions form repressive domains that interact in 3D to assemble repressive nuclear compartments. Here, we used multiplexed chromatin imaging to investigate whether Pc compartments involve the clustering of multiple Pc domains during Drosophila development. Notably, 3D proximity between Pc targets is rare and involves predominantly pairwise interactions. These 3D proximities are particularly enhanced in segments where Pc genes are co-repressed. In addition, segment-specific expression of Hox Pc targets leads to their spatial segregation from Pc repressed genes. Finally, non-Hox Pc targets are proximal in regions where they are co-expressed. These results indicate that long-range Pc interactions are temporally and spatially regulated during differentiation and development but do not involve clustering of multiple distant Pc genes.

Although the polygonal shape of epithelial cells has been drawing the attention of scientists for several centuries, only a decade and a half ago it was demonstrated that distributions of polygon types (DOPTs) are similar in proliferative epithelia of many different plant and animal species. In this study, we show that hyper-proliferation of cancer cells disrupts this universal paradigm and results in randomly organized epithelial structures. Examining non-synchronized and synchronized HeLa cervix cells, we suppose that the spread of cell sizes is the main parameter controlling the DOPT in the cancer cell monolayers. To test this hypothesis, we develop a theory of morphologically similar random polygonal packings. By analysing differences between tumoural and normal epithelial cell monolayers, we conclude that the latter have more ordered structures because of their lower proliferation rates and, consequently, more effective relaxation of mechanical stress associated with cell division and growth. To explain the structural features of normal proliferative epithelium, we take into account the spread of cell sizes in the monolayer. The proposed theory also rationalizes some highly ordered unconventional post-mitotic epithelia.

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., Phys. Rev. Res. 2, 033377 (2020).

I'll present the computation of a D-instanton induced superpotential in an orientifold Calabi-Yau compactification of type II string theory using a direct worldsheet approach.

Euclidean D-branes wrapped on non-trivial cycles of a Calabi-Yau threefold are known to affect the metric on the hypermultiplet moduli space determining the effective action of type II strings on such manifolds. After reviewing the existing results on the instanton corrected metric following from a combination of constraints imposed by supersymmetry and dualities, I'll show how the D-instanton effects can be computed by a direct worldsheet approach. It required solving several conceptual and technical problems and has recently been extended to compactifications with lower supersymmetry. The talk is based on joint work with A. Sen and B. Stefanski.