Funded PhD project: optogenetic control of FGF and Eph signaling pathways during ascidian embryogenesis

Context:

Cell-cell communication plays a central role in the coordination of morphogenesis and fate specification. Most components of the major signalling pathways have been identified. We however lack a quantitative understanding, in time and space, of the dynamics of signal transduction from the membrane to the nucleus. The CRBM Tunicate embryology Research Team uses molecular and 3D + time live imaging approaches to study this process during ascidian embryogenesis.

The PhD project:

One of our major projects combines experimental and mathematical modelling approaches to produce a quantitative model of the information flow between membrane and nucleus for two major signal transduction pathways.

We are looking for a PhD student to develop an optogenetic control strategy for the FGF/SOS/Ras/ERK and Eph/RasGAP/Ras signaling pathways. This approach will open the way to a variety of questions including: how long does signal transduction take from the membrane to the nucleus? during which phase(s) of its cell cycle is the cell competent to respond to receptor activation? what is the minimum activation time of the receptor needed to produce a stable nuclear response? what is the function linking the activation level of the receptor and that of ERK? The experimental results will be integrated into a mathematical model, in collaboration with theoreticians, which will provide suggestions for further experiments.

Training:

This project is mostly experimental. It will give the selected student a solid expertise in embryology (microinjections, in vitro fertilization…), signal transduction and advanced light-sheet imaging. In addition, the PhD student will frequently interact with our computer science collaborators, the MOSAIC and ICAR teams.  Participation in public outreach actions (Science festivals, My Thesis in 180 seconds, …) will be encouraged.

Necessary skills:

• Master training in cell biology or development, with a strong interest for embryonic development
• An interest in mathematical modelling (no specific mathematical knowledge needed).
• A first experience in molecular cloning and confocal/light-sheet microscopy of live samples would be appreciated.
• An experience in RNA or proteins microinjection into oocytes would be a plus but is not required.
• No Knowledge of French required. Working knowledge in written / spoken English needed.

Application:

This project can be joined directly as a PhD student in fall/winter 2019, or as a Master intern in winter 2019, the PhD only starting in fall 2020. Funding is for 3 years.

Informal enquiries can be made to Patrick Lemaire (patrick.lemaire@crbm.cnrs.fr). Formal applications are through the CNRS employment portal.

About the host institute:

The host research team is located at a major Cell Biology institute in Southern France, the CRBM (CNRS /U. Montpellier). All seminars and meetings are in English. The institute has a very well-equipped Imaging core facility, hosting a Luxendo MuViSPIM microscope on which lightsheet microscopy experiments will be carried out.

References linked to the project:

Leggio, B; Laussu J; Carlier, A; Godin, C; Lemaire, P and Faure, E (2019) MorphoNet: An interactive online morphological browser to explore complex multi-scale data. Nat Commun. 10(1):2812

Guignard*, U.-M. Fiuza*, B. Leggio, E. Faure, J. Laussu, L. Hufnagel, G. Malandain, C. Godin#, P. Lemaire# (2017) Contact-dependent cell communications drive morphological invariance during ascidian embryogenesis. bioRxiv 238741 https://www.biorxiv.org/content/early/2017/12/24/238741

U-M Fiuza, T. Negishi, A. Rouan, H. Yasuo, P. Lemaire  Nodal and Eph signalling relay drives the transition between apical constriction and apico-basal shortening during ascidian endoderm invagination (2018) bioRxiv 418988 https://www.biorxiv.org/content/early/2018/09/15/418988

Lemaire P. (2011) Evolutionary crossroads in developmental biology: the tunicates, Development, 138(11):2143-52.

Tassy, O., Daian, F., Hudson, C., Bertrand, V., Lemaire, P. (2006) A quantitative approach to the study of cell shapes and interactions during early chordate embryogenesis. Current Biology 16:345-58

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