PhD studentship in France
A PhD position is opened in the lab of Nathalie Dostatni (Curie Institute, France).
The call is partly funded by the European Community and applicants must not have lived/worked/studied in France more than 12 months between 15 January 2015 and 15 January 2018. Also, they must have obtained their Master degree after January 2016. Application must be done on line at the following link: https://enseignement.curie.fr/en/content/current-call-applications and the deadline for application is January 18th (with possible extension to January 25th).
Description of the PhD thesis project
Morphogen gradients are used to establish polarity along embryonic axes or within organs. In these systems, positional information stems from the morphogen concentration detected by each cell in the target tissue and mediates the determination of cell identity through the expression of specific sets of target genes. Although the critical role of these gradients is now well described, how they can provide reproducible transcription patterns given the inherent stochastic nature of transcription remains unclear.
To address this question, we recently used the MS2/MCP approach to fluorescently tag RNA and study the dynamics of transcription downstream of the Bicoid morphogen gradient in living fruit fly embryos. Analysis of fluorescent time traces indicated that despite high variability in promoter functioning, loci of the main Bicoid target were able to measure their position along the length of the embryo with high precision in a very short time.
To understand how measurements of Bicoid concentration are achieved so rapidly, we will perturb the system in various genetic backgrounds and use the MS2/MCP approach to record the temporal transcription dynamics at single target locus in each nucleus of whole embryos. Using statistical physics and inference algorithms on the data collected with confocal microscopy, we will extract the characteristic parameters of the transcription kinetics of the promoter upon these perturbations. This will allow determining how maternally expressed transcription factors and/or chromatin regulators contribute to the rapid and robust responsivity of the system.
This project is highly interdisciplinary and combines cutting edge imaging with the power of fruit fly genetics. It is at the interface between molecular/developmental biology, biophysics and systems-biology.