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Propositions de stage, thèse ou post-doc

Master 2 internship (2016-2017) and PhD (2017-2020) proposal: Physical modeling of a developing biological tissue

Field: Theoretical and computational soft condensed matter physics and biophysics.

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Physical modeling of a developing biological tissue

Biological tissues, especially during embryogenesis, are a fascinating example of an active material, whose mechanical and structural properties evolve continually. The evolution of these properties result in new shapes (morphogenesis). It is more and more established that mechanical stress in tissues is an essential ingredient of biological signaling: it combines with chemical signals to let tissue cells locate themselves, which affects their fate (cellular type).


Apoptosis drives fold formation in Drosophila leg (Magali Suzanne, Toulouse).
With this internship, our goal is to simulate the behaviour of a few cells in such a tissue for some precise phenomena, in collaboration with a biologist experimental team, depending on opportunities and on the candidate's preferences.


Simple simulation with actin belt and complex cortex rheology.
One possibility is to focus on apoptosis and on its mechanical role which has been evidenced during Drosophila leg development by a team in Toulouse (Magali Suzanne, see (1) and photo). We will use a detailed and tunable mechanical model. Our current code contains a non-trivial rheology of the cellular cortex and a dynamic evolution of cell-cell adhesion inspired by molecular mechanisms. The internship will consist in incorporating additional ingredients specific to apoptosis in order to identify those that are essential to reproduce the observed mechanical transformations.

On the long term (thesis work), internal cell mechanisms that are essential to its interaction with neighbouring cells within a tissue will be included gradually. This will be used to specify our generic continuum model (2) and to infer (3) the macroscopic rheology.

(1) B. Monier, M. Gettings, G. Gay, T. Mangeat, S. Schott, A. Guarner, M. Suzanne, Nature (2015) 518, 245-248
(2) S. Tlili, C. Gay, F. Graner, P. Marcq, F. Molino, P. Saramito, Eur. Phys. J. E (2015) 38, 33-63 ; 38, 115
(3) V. Nier, S. Jain, C. T. Lim, S. Ishihara, B. Ladoux, P. Marcq, Biophys. J. (2016) 110 (7), 1625-1635
Candidate
The successful candidate will either be familiar with biophysics or soft matter physics, or with applied mathematics and numerical simulations, for instance in C++ or in python and will be eager to interact with experimentalists in order to reorient the simulation ingredients.
Supervisor:
Cyprien GAY cyprien.gay@univ-paris-diderot.fr 01 57 27 62 53
Co-supervisors:
Philippe MARCQ philippe.marcq@curie.fr 01 56 24 64 72
François MOLINO francois.molino@igf.cnrs.fr 04 67 14 32 08

Collaboration:
Guillaume GAY at DAMCB
Magali SUZANNE, Toulouse.

Location:
Université Paris Diderot, Bâtiment Condorcet
Laboratory name: Matière et Systèmes Complexes (MSC)
CNRS identification code: UMR 7057.
Thesis possibility after internship: YES

Funding
Internship: usual (legal) funding when longer than two months (ca. 500€/month).
PhD funding possibilities:
1. with “école doctorale” (concours),
2. with région Ile-de-France (Institut des Systèmes Complexes),
3. with CIFRE (corporate co-funding).

Master 2 internship (2016-2017) and PhD (2017-2020) proposal: Statistical inference of tissue rheology

Field: Theoretical and computational soft condensed matter physics and biophysics.

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Statistical inference of tissue rheology

Rheology is the study of the flow of matter. When cell-cell adhesion is strong, living tissues form a cohesive material, amenable to hydrodynamic descriptions. When cells are motile, their collective migration spontaneously generates tissue flow. During morphogenesis, tissue size and shape emerge through multi-scale feed-backs involving both genes and mechanics. As a first, crucial step, one needs to determine the tissue rheology, or how cell-generated displacements and forces produce tissue deformations. Tissue rheology involves mechanical ingredients, but must often take into account additional biological ingredients, such as contractility, polarity, cell proliferation and cell death, or the densities of relevant proteins such as morphogens and molecular motors [1].

Direct modeling approaches postulate a tissue rheology, then compare predictions with data. Since Bayesian inversion now allows to estimate the tissue stress field [2,3], we propose to investigate inverse approaches to tissue constitutive equations, and to determine tissue rheology from experimental data thanks to statistical inference. This approach has been successful for homogeneous cellular aggregates: we wish to extend it to epithelial cell monolayers where spatial degrees of freedom are relevant.
The first objective of the project is to combine stress field estimates with kinematic quantifiers of tissue dynamics to infer the constitutive equations of a tissue in physiological conditions, and determine the relevant material parameters. We will use experimental data measured in in vitro (cell monolayers) and/or in vivo systems (epithelia of developing organisms), as well as numerical data from simulations of cell-based models of epithelia.

This internship/thesis will involve analytical and numerical calculations, as well as experimental data analysis, at the interface between theoretical soft matter physics, mechanobiology, and statistics. No prior knowledge of the biology of tissues is required.

The project will necessitate a strong desire to collaborate with experimentalists.
[1] S. Tlili, C. Gay, F. Graner, P. Marcq, F. Molino and P. Saramito, Mechanical formalisms for tissue dynamics , Eur. Phys. J. E 38, 33 (2015)
[2] S. Ishihara and K. Sugimura, Bayesian inference of force dynamics during morphogenesis , J. Theor. Biol. 313C 201-211 (2012)
[3] V. Nier, S. Jain, C.T. Lim, S. Ishihara, B. Ladoux and P. Marcq, Inference of internal stress in a cell monolayer, Biophys. J. 110 1625-1635 (2016)
Supervisor: Philippe MARCQ philippe.marcq@curie.fr 01 56 24 64 72
Co-supervisor: Cyprien GAY cyprien.gay@univ-paris-diderot.fr 01 57 27 62 53.
Location: Physico-Chimie Curie, Institut Curie, 11 rue Pierre et Marie Curie, 75005 Paris. Thesis possibility after internship: YES

PhD funding possibility: École Doctorale (concours).

Students

  • Étienne Moisdon (PhD student, starting Sept 2017).
  • Pierre Seez (M2 student, starting Sept 2017).

Former students

 
etudiants/sujets.txt · Dernière modification: 2018/02/03 14:09 par cgay
 
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