Clathrin-mediated endocytosis (CME) consists of the formation of a vesicle out of a flat membrane in eukaryotes. When membrane tension and/or turgor pressure are high, actin dynamics is required to produce the forces required to invaginate the membrane and pinch it off into a vesicle. However, how the actin meshwork produces forces at the molecular level has remained elusive, because endocytic structures are intrinsically transient, out of equilibrium, and diffraction limited. In this seminar, I will present results from mathematical modeling and experiments in yeast demonstrating that actin polymerization alone cannot produce sufficient force to invaginate the plasma membrane. I will also present new force production mechanisms by the actin meshwork that are not exclusively based on polymerization, and are relevant to other subcellular processes involving actin and membranes.  

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Traumatic injury, birth defects, and even cancer and aging: most biomedical problems would be resolved if we had control over 3D living anatomy. In order to control what structures cells build, we need to understand how cellular collectives make decisions - how do groups of cells know what to build and when to stop?  My lab works at the intersection of developmental biology, computer science, and cognitive science. By building molecular tools to read and write the bioelectric patterns in coupled cellular networks (all tissues, not specifically neurons), we have uncovered a fascinating system of physiological "software" that runs on genome-specified cellular hardware. These bioelectric networks store the setpoints for anatomical homeostasis, and serve as the primitive memory of the tissue for anatomical target morphology. We have shown how this information can be modified in vivo, to exert remarkable control over growth and form. We are now creating machine learning systems to assist with the design of electroceuticals - blends of ion channel drugs guided by computational models of bioelectric circuits that restore correct voltage prepatterns and lead to repair. Our computational and biophysical approaches to modulating bioelectrical pattern memories in vivo may contribute to the repair of birth defects, induction of limb regeneration, and tumor normalization. 

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L'objectif général de ce 3e cours de biologie cellulaire et cancer est de couvrir différents sujets de la biologie cellulaire et de la biologie des cellules cancéreuses, y compris la croissance des cellules et des tissus, la signalisation cellulaire, la division cellulaire, l'organisation des cellules et des tissus à différents niveaux : moléculaire, cellulaire et dans l'organisme vivant. En outre, nous aurons une session consacrée à la physique des tissus.

Ce cours est prévu en présentiel à Paris. Selon les conditions sanitaires et les recommandations du gouvernement français en mai 2021, il pourra se tenir entièrement à distance ou sur un mode hybride.

Zebrafish and chicken embryo can easily be cultured in vitro from zygote to birth, and new microscopy techniques give access to organs and limbs formation in the context of the whole developing embryo. But no mammal has been born in vitro, starting from a zygote, up to now and imaging a process of the developing embryo from the beginning to the end remain a challenge. To address this problem, wouldn’t another model than the mouse be more suitable for mammalian developmental biology?

The grey-short tailed opossum (Monodelphis domestica) is a small marsupial, of a size comparable to a rat. Its embryos implant in the uterus after 10 days of development spent floating in the reproductive tracts. By that time, the embryo is reaching the end of the somatogenesis stage and the heart is already beating.  Implantation itself is superficial, especially compared to the mouse, and last for around three days, before the birth of a “not-so-finished new-born” called a joey.

 We achieved for the first time microinjection of mRNA in the opossum zygote and 4-cell embryo, followed by live-imaging on a confocal microscope. We tried culture of the different stages to reveal which processes can be accessed in vitro, and identify the problems to overcome to use the opossum to address all the different questions of developmental biology, starting from the first question: the establishment of the first lineages in the mammalian embryo, in the context of an embryo without inside-outside cue, as the marsupial blastocyst is unilaminar.

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Tumors employ complex, multi-scale cellular and molecular interactions that evolve over the course of therapeutic response. The changes in these pathways enables tumors to overcome therapeutic regimens, and ultimately acquire resistance. New molecular profiling technologies, including notably single cell technologies, provide an unprecedented opportunity to characterize these molecular relationships. However, interpreting the specific cellular and molecular pathways in therapeutic response requires complementary computational analysis methods. We developed an unsupervised learning method, CoGAPS, that employs Bayesian non-negative matrix factorization to disentangle distinct biological processes from high-throughput molecular data. Notably, this algorithm discovers dynamic compensatory signaling in acquired therapeutic resistance from time course bulk RNA-seq data and novel NK cell activation in anti-CTLA4 response from post-treatment scRNA-seq data. To further demonstrate that the inferred pathways are biological rather than computational artifacts, we developed a complementary transfer learning method to relate learned patterns between datasets. We demonstrate that this approach identifies robust molecular processes between model systems and human tumors and enables multi-platform data integration to delineate the drivers of therapeutic response and resistance.