Postdoctoral position opening (starting October 2022 - early 2023):
ORGANISATION, STABILITY AND RIGIDITY OF CONFLUENT CELL MONOLAYERS
Left: real biological epithelium. Right: numerical model (cellular Potts model).
PROJECT:
Biological tissues such as epithelia are made of confluent cells tiling perfectly the available space, i.e. without gaps or overlaps. However, their structure is not static, but evolves continuously because of cell activity, cell division (mitosis), cell death (apoptosis) or extrusion. From a physicist's perspective, they are active cellular materials, a part of dense active matter, a fast growing area of scientific research.
In spite of these active structural rearrangements, a stable organization at the macroscopic scale is essential to preserve the integrity of the tissue as well as its biological function.
Because of the high deformability but low compressibility of cells, local organization fluctuations are coupled in a non-trivial way. Using computational tools (Cellular Potts Model and/or Vertex Model) and theoretical techniques, we aim at understanding how structural fluctuations and defects affect — but also give insight to — the integrity and the rigidity of confluent cell monolayers. As an illustration, we are currently investigating the stability and fluctuations of the boundary between two active epithelial tissues.
FUNDING AND SCIENTIFIC ENVIRONMENT:The project is funded by the LabEx SEAM. The initial appointment is for 1 year, starting anytime between October 2022 and early 2023. Financial support for a second year is being considered. The recruited post-doc will benefit from a world-class interdisciplinary environment within the MSC lab which renowned for its expertise in soft condensed matter, biophysics and physics of out-of-equilibrium systems: http://www.msc.univ-paris-diderot.fr/?lang=en
SKILLS:We seek motivated researchers with computational and theoretical skills, and with some expertise in soft condensed matter theory, statistical physics or biophysics.
CONTACT:
Interested candidates can apply by sending cover letter, CV, and email addresses of two references to marc.durand@univ-paris-diderot.fr. Please do not hesitate to contact me for any informal inquiry regarding this offer.
Download the postdoctoral position opening description in english
Biological tissues such as epithelia are made of confluent cells tiling perfectly the available space, i.e. without gaps or overlaps. However, their structure is not static, but evolves continuously because of cell activity, cell division (mitosis), cell death (apoptosis) or extrusion. From a physicist's perspective, they are active cellular materials, a part of dense active matter, a fast growing area of scientific research.
In spite of these active structural rearrangements, a stable organization at the macroscopic scale is essential to preserve the integrity of the tissue as well as its biological function.
Because of the high deformability but low compressibility of cells, local organization fluctuations are coupled in a non-trivial way. Using computational tools (Cellular Potts Model and/or Vertex Model) and theoretical techniques, we aim at understanding how structural fluctuations and defects affect — but also give insight to — the integrity and the rigidity of confluent cell monolayers. As an illustration, we are currently investigating the stability and fluctuations of the boundary between two active epithelial tissues.
FUNDING AND SCIENTIFIC ENVIRONMENT:The project is funded by the LabEx SEAM. The initial appointment is for 1 year, starting anytime between October 2022 and early 2023. Financial support for a second year is being considered. The recruited post-doc will benefit from a world-class interdisciplinary environment within the MSC lab which renowned for its expertise in soft condensed matter, biophysics and physics of out-of-equilibrium systems: http://www.msc.univ-paris-diderot.fr/?lang=en
SKILLS:We seek motivated researchers with computational and theoretical skills, and with some expertise in soft condensed matter theory, statistical physics or biophysics.
CONTACT:
Interested candidates can apply by sending cover letter, CV, and email addresses of two references to marc.durand@univ-paris-diderot.fr. Please do not hesitate to contact me for any informal inquiry regarding this offer.
Download the postdoctoral position opening description in english
M2 internship and funded PhD thesis (2020):
Morphogenesis of the vascular network of a biological model (P. Polycephalum):
Growth, self-organization, and optimization
Like E. Coli, C. Elegans or Drosophila, Physarum Polycephalum is a model organism intensively studied by the scientific community. In its vegetative phase, called plasmodium, this organism is made of thousands of undifferentiated cells fusing in a single, multinuclear cell, and can reach macroscopic sizes (dozens of cm²). This organism then develops a tubular network in which oscillatory flows (with period ~ 1 minute) are generated by the contraction of the membranous layer surrounding the “veins”. The role of this transport network is to supply the diffusive flows which are too slow to efficiently transport oxygen, nutrients, or waste through the whole cell. Physarum Polycephalum is likely the simplest organism with a vascular network.
The second function of this network is to efficiently transport the body mass during the growing stage or displacement of the cell. This requires from this organism, deprived from central nervous system, a local control of the sol-gel transition of the cytoplasm, and a synchronization of the contractile activity in the whole organism in order to generate a contractile wave traveling from one side of the cell to the other.
In spite of its apparent simplicity, the growth of the tubular network shares common features with the development of vascular systems in higher organisms, or with the mechanisms that take place in the irrigation of tumors. In particular, one can clearly identify two stages in the development of the plasmodium: a growing phase during which P. Polycephalum explores its environment covering all the plane with a very dense and ramified tubular network. Then a reorganizing phase during which the organism seems to follow an optimization scheme: the network is less and less reticulated. Eventually, the organism is then simply reduced to a few tubular elements directly connecting the different sources of food. Besides, separate plasmodia of same strain can merge together to create a larger plasmodium. Their networks connect to each other, allowing to exchange cytoplasm, nuclei, vesicles, etc.
From a physicist’s perspective, the plasmodium is an active gel that is able, at short times, to generate and adapt contractile waves along the veins to generate peristaltic flows, and at long times to control actively its sol-gel transition to modify the network architecture.
During this internship, we will study the coupling between the contractile activity and the formation of the tubular network in the early stage of the plasmodium development, called microplasmodium. At this stage (size~200 µm), the plasmodium can be seen as an active drop with an erratic contractile activity at the beginning. This activity generates local heterogeneities of shear strain, leading to sol-gel transition locally within the cytoplasm, which in turn will affect the local contractile activity of the microplasmodium. Progressively, a primitive network of flowing material emerges within the gel.
In practice, we will measure simultaneously the thickness field of the microsplasmodium using transmitted light imaging, and the velocity field within the microplasmodium using standard velocimetry techniques, in order to highlight the feedback role of the flow in the contractile activity and the synchronization phenomena. We will also study how the addition of inhibitors of contractile activity affect the network development.
At long term (PhD), we will identify the mechanisms involved in the network formation and evolution during the reorganization and optimization of the network, and during the merging of the networks of two plasmodia in contact.
Download the thesis/internship opportunity in english
The second function of this network is to efficiently transport the body mass during the growing stage or displacement of the cell. This requires from this organism, deprived from central nervous system, a local control of the sol-gel transition of the cytoplasm, and a synchronization of the contractile activity in the whole organism in order to generate a contractile wave traveling from one side of the cell to the other.
In spite of its apparent simplicity, the growth of the tubular network shares common features with the development of vascular systems in higher organisms, or with the mechanisms that take place in the irrigation of tumors. In particular, one can clearly identify two stages in the development of the plasmodium: a growing phase during which P. Polycephalum explores its environment covering all the plane with a very dense and ramified tubular network. Then a reorganizing phase during which the organism seems to follow an optimization scheme: the network is less and less reticulated. Eventually, the organism is then simply reduced to a few tubular elements directly connecting the different sources of food. Besides, separate plasmodia of same strain can merge together to create a larger plasmodium. Their networks connect to each other, allowing to exchange cytoplasm, nuclei, vesicles, etc.
From a physicist’s perspective, the plasmodium is an active gel that is able, at short times, to generate and adapt contractile waves along the veins to generate peristaltic flows, and at long times to control actively its sol-gel transition to modify the network architecture.
During this internship, we will study the coupling between the contractile activity and the formation of the tubular network in the early stage of the plasmodium development, called microplasmodium. At this stage (size~200 µm), the plasmodium can be seen as an active drop with an erratic contractile activity at the beginning. This activity generates local heterogeneities of shear strain, leading to sol-gel transition locally within the cytoplasm, which in turn will affect the local contractile activity of the microplasmodium. Progressively, a primitive network of flowing material emerges within the gel.
In practice, we will measure simultaneously the thickness field of the microsplasmodium using transmitted light imaging, and the velocity field within the microplasmodium using standard velocimetry techniques, in order to highlight the feedback role of the flow in the contractile activity and the synchronization phenomena. We will also study how the addition of inhibitors of contractile activity affect the network development.
At long term (PhD), we will identify the mechanisms involved in the network formation and evolution during the reorganization and optimization of the network, and during the merging of the networks of two plasmodia in contact.
Download the thesis/internship opportunity in english
Thesis / Internship Opportunity (2020):
Contour fluctuations in soft cellular systems
Figure 1: Contour fluctuations of a cell monolayer.
Foams, emulsions, and biological tissues are examples of soft cellular systems: they are made of units (bubbles, drops, cells) with high deformability but low compressibility, interacting through attractive adhesive interactions and soft steric repulsions. When highly compacted, they tile perfectly the available space (3D) or plane (2D), i.e. without gaps or overlaps [1].
In the case of biological tissues, the structure is essential for their function. Unlike foams and emulsions, biological tissues are active cellular systems: they consume (chemical) energy to produce motion and fluctuations of the interfaces.
Because of the low compressibility of the cellular domains, interface fluctuations are coupled in a non-trivial way. The aim of the present study is to analytically and numerically investigate the contour fluctuations (lengths and heights) of two-dimensional active cellular systems. We will first characterize the fluctuations driven by thermal agitation (thermal equilibrium), then investigate the fluctuations caused by active processes such that those taking place in a epithelium.
Of special interest, we want to investigate whether the spectrum of fluctuations captures useful information on the structural characteristics of the pattern (such as dispersity in size and side number of the cellular domains) and/or its mechanical properties.
Required skills: the candidate should have a strong inclination for theory (especially statistical physics) and numerical simulations.
[1] M. Durand and J. Heu, arXiv preprint arXiv:1910.02742, Physical Review Letters 123, 188001 (2019).
Download the thesis/internship opportunity in english
In the case of biological tissues, the structure is essential for their function. Unlike foams and emulsions, biological tissues are active cellular systems: they consume (chemical) energy to produce motion and fluctuations of the interfaces.
Because of the low compressibility of the cellular domains, interface fluctuations are coupled in a non-trivial way. The aim of the present study is to analytically and numerically investigate the contour fluctuations (lengths and heights) of two-dimensional active cellular systems. We will first characterize the fluctuations driven by thermal agitation (thermal equilibrium), then investigate the fluctuations caused by active processes such that those taking place in a epithelium.
Of special interest, we want to investigate whether the spectrum of fluctuations captures useful information on the structural characteristics of the pattern (such as dispersity in size and side number of the cellular domains) and/or its mechanical properties.
Required skills: the candidate should have a strong inclination for theory (especially statistical physics) and numerical simulations.
[1] M. Durand and J. Heu, arXiv preprint arXiv:1910.02742, Physical Review Letters 123, 188001 (2019).
Download the thesis/internship opportunity in english