Closing Date: 15 March 2021
Applicants are sought for two 3-year doctoral contracts to work on developmental variability and canalization in Ascidians.
Context:
Within each animal species, embryonic development is highly reproducible, ensuring the production of a complex organism with precisely arranged and shaped organs and tissues. This constancy of embryogenesis against genetic polymorphism and fluctuating environmental conditions is critical for the perpetuation of the species, and has been referred to as developmental canalization (Waddington, 1942).
Among animals, nematodes and ascidians (Lemaire, 2011), exemplify the most extreme form of developmental canalization: the quasi-invariant behaviour of individual embryonic cells, such that each cell can be named unambiguously and found across individuals of the same or related species. Such organisms constitute attractive models to unravel the still elusive molecular basis of canalization.
The two proposed projects will explore how these variations are buffered, or canalized, in one class of animals with a highly stereotyped embryogenesis, the ascidians (Lemaire, 2011). The links will bring you to the project page of the CBS2 doctoral school.
Candidates are encouraged to
contact by May 1st the future supervisors:
patrick.lemaire@crbm.cnrs.fr (both projects) and
gregoire.malandain@inria.fr (computer science project) by sending a CV with exam rankings, a motivation letter and the e-mail of two potential academic referees.
Application deadline of selected candidates to the doctoral schools will be May 9
We will focus on the FGF/Ras/ERK pathway, the major fate-inducing pathway during early ascidian embryogenesis. Using a fluorescent reporter (Cova et al., 2017) and lightsheet imaging, we will first quantify in live embryos the variability of the dynamics of the activation downstream component of the pathway, ERK, between individuals of the same species and between species, during normal development. This initial set of measurements will be used as a reference to identify molecular or environmental perturbations that increase or decrease the variability of ERK signalling.
We will first test Waddington’s “canalization” proposal that any perturbation of wild-type development increases phenotypic variance (Waddington, 1942). We will then analyse the effect of changes in temperature and salinity on ERK signalling precision, and test the hypothesis that the Hsp90 chaperone acts as a phenotypic buffering mechanism during development (Zabinsky et al., 2018).
Finally, we will test the hypothesis that the precision of ERK activation may result from positive or negative feedback loops acting within the FGF/ras/ERK signalling pathway. Taken together the results obtained during this project will establish the ascidian embryos as a paradigm to study phenotypic robustness during development.
(co-supervised with Grégoire Malandain, INRIA, Sophia Antipolis)
The aim of this computational biology project is to develop a conceptual framework to quantify developmental variability, with single cell resolution, within and between ascidian species and to use this framework to explore the spatio-temporal structure of this variability.
The starting point of this project is the availability of a collection of 12 digitalized wild-type embryos in which each cell was systematically segmented and tracked every two minutes for up to 5 cell divisions during embryogenesis. This digitalization allowed to associate to each individual cell a set of properties defining their embryological (fate), geometrical (volume, surface) and topological (neighborhoods and surface of contact with neighbors) features (Guignard et al., 2018). For an example
see our work among the Node’s Xmas GIFs 2018.
To characterize the temporal and spatial structure of the developmental variability of these embryos, we propose to construct a conceptual framework describing average ascidian development and to quantify deviations from this average.
For this, we will construct a toolbox that will make it possible to: 1) Align digital embryos in time and space; 2) Construct average digital embryos for a given (sub)population and/or species; 3) Characterize the geometric and topological variability of a population of 3D shapes.
We will use this toolbox to address two different types of issues. The first is of biological nature and relates to the expected pattern of variability across time. The second is more methodological, and aims at improving our current segmentation strategy by including knowledge gained from previously-segmented embryos.
References:
Cova, C. de la, et al. (2017). A Real-Time Biosensor for ERK Activity Reveals Signaling Dynamics during C. elegans Cell Fate Specification. Dev. Cell 42, 542-553.e4.
Guignard, L., Fiuza, U.-M., et al. (2018). Contact-dependent cell communications drive morphological invariance during ascidian embryogenesis. bioRxiv 238741.
Lemaire, P. (2011). Evolutionary crossroads in developmental biology: the tunicates. Development 138, 2143–2152.
Waddington, C. H. (1942). canalization of development and the inheritance of acquired characters. Nature 150, 563–565.
Zabinsky, R. A., et al. (2018). It’s not magic – Hsp90 and its effects on genetic and epigenetic variation. Semin. Cell Dev. Biol.
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