CELLCOORDINATION
Temporal coordination of gene expression during development
| Coordinatore | THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Organization address
address: The Old Schools, Trinity Lane contact info |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 221˙606 € |
| EC contributo | 221˙606 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2013-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 2014 |
| Periodo (anno-mese-giorno) | 2014-06-01 - 2016-05-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Organization address
address: The Old Schools, Trinity Lane contact info |
UK (CAMBRIDGE) | coordinator | 221˙606.40 |
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Obiettivo del progetto (Objective)
'During embryonic development cells coordinate spatiotemporal patterns of gene expression. A prominent example of this coordination is found in the gastrulation of amniotes, where Brachyury (Bra), a transcription factor, is synchronously and transiently expressed in a localized population, the Primitive Streak (PS). Even though the current view is that a morphogen gradient drives the spatial arrangement of Bra expression, the precise mechanisms controlling timing and coordination of cells remain to be elucidated. Recent evidence of the existence of RNA polymerase II (Pol II) pausing control in the bra locus in differentiating mammalian cells prompts the question of whether this mechanism is involved in the coordination of Bra expression. In Drosophila, Pol II pausing has been associated with developmental control genes, where it has been suggested to enhance the synchrony of expression in response to stimuli, and consequently increasing cell coordination during morphogenesis. Despite Pol II pausing is pervasive in mammalian embryonic stem cells (ESCs), its role in the fast and coordinated activation of gene expression has non been addressed yet.
Here I propose to study how coordination of Bra expression is attained in differentiating mouse ESCs, which are known to recapitulate the cellular and molecular events observed in the PS. I will combine live cell imaging with theoretical modelling, to investigate the temporal dynamics of Bra activation. I surmise that Pol II pausing modulates stochasticity in the response and thus affects cellular coordination in Bra expression. To test this hypothesis, I will modify the levels of pausing in the bra promoter and correlate them with achieved cellular coordination. The results of this project will deepen our insight in the mechanisms underlying cellular synchronization during development and may uncover more general principles that govern the way in which mammalian cells coordinate their decisions at the tissue level.'