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Morphogenesis In Vitro

Reference : PhD Daniel RIVELINE

Offer publication : April 6, 2016

Tissue changes their shapes during the development of embryos. Cells proliferate, reorganize their spatial localisations, change their neighbours and their shapes. Since few years, these major reorganisations have attracted an expanding interest of physicists and biologists : the evolution of tissues looks similar to the dynamics of foams. With a revisited formalism, it has been established that the acto-myosin complexes probe mechanically the edges of cells, and these local phenomena are translated into global reorganizations of tissues. Transformations of tissues can be written in equations and simulated in silico. Local cell shapes and global organisations follow rules that can be tested and predicted in certain cases.

In addition to physical laws, these phenomena implies also the Rho signaling pathways which regulate the activities of myosins, in particular, kinases and phosphatases. Disentangling the contributions and interplays between mechanics and signaling is part of a field in expansion, Mechanobiology, in France and abroad, a domain at the Interface between Physics and Biology.
However, it is rare that tissues in formation are isolated from model systems characterised in vivo. The neighbouring organs can influence the fate of tissues. In fact, it is probable that tissues characterised so far in vivo evolve under the mechanical influence of their environments, and not along their
own isolated rules of morphogenesis.

The topic for the PhD will try to reproduce these steps outside the embryo in vitro and in silico, while comparing the cell movements with the dynamics observed in vivo. Epithelial cells will be placed on microfabricated motifs with 2D and 3D shapes mastered, flat surfaces, spheres, cylinders, with controlled dimensions. With the application or not of external mechanical constraints, local or global, we will mimic elongation and gastrulation. We expect that certain steps will be amplified depending on the external and internal constraints. The nature of the mechanical stimuli will be probed, specific shapes are expected, and the visualisation of cells in dynamics will permit to characterize the measured tissue dynamics.
When these phenomena will have been reproduced in vitro, the cells will be modified locally or globally through their contractility, through the Rho pathways, adherens junctions, and focal contacts. We expect predictable changes in shapes depending on these variations. During later phase of the PhD, organoids will be prepared in collaboration with biologists specialised in this field at IGBMC, and the dynamics will be compared to the systems under study. The results will be compared to the same phenomena observed in model systems at IGBMC, Drosophila, C. elegans, Zebrafish, mouse. This study will involve cell biology, developmental biology, microfabrication, imaging at high resolution, modeling. The framework of IGBMC is ideal for performing these experiments. In addition, the new Master of the University of Strasbourg http://www.cellphysics-master.com/ prepares optimally the students to this type of topic in expansion throughout the world. Finally, the team has obtained new results on this topic in collaborations with biologists and physicists in France and abroad.

- WISHED SKILLS : It would be good that the candidate is open to collaborations at the Interfaces between Physics and Biology. His/Her education will be in Biology or in Physics. He/She will interact will collaborators of various scientific backgrounds, theorists and experimentalists. He/She should show some quality of adaptation to work in collaborative networks.

EXPERTISES WHICH WILL BE ACQUIRED DURING THE TRAINING : The candidate will learn to manipulate cell, and will become an expert in microfabrication in the clean room. He/She will practice regularly imaging at high resolution with various methods, as well as mechanical perturbations of the systems. He/She will learn to translate ideas expressed in theoretical physics into experimental measures on living matter.

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Application Deadline : Dec. 31, 2016

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