The mechanisms powering the transition from one cell state to another are the central engine of embryonic development. Genetic analysis over the last twenty years has provided us with a catalogue of genes and proteins that can be linked in linear and time dependent manners to specific states and transitions in this process. However this picture, characterized by complex charts of univocal relationships between different genes, is static and rigid and contrasts with the plasticity displayed by cells in many processes, in particular during repair and regeneration. The early mammalian embryo and the closely related ES cells provide extreme examples of this in the form of toti- and pluri-potency i.e. the maintenance of an open uncommitted state from which all cell types emerge. Understanding the molecular basis of these uncommitted states and the way they are established and regulated will not only provide a deeper insight into the operation of biological systems but will also new targets for regulation and therapies. This project revolves around the hypothesis that the plasticity displayed by cells in developmental and regulative processes is associated with dynamical cellular heterogeneities generated by transcriptional noise: phenotypic variability in genetically identical cells that arises from stochastic fluctuations during transcription and translation. Specifically I propose to provide measurements and analysis of gene expression noise in mammalian cells, its origin, regulation and use using ES cells and early mouse embryos as experimental systems.
Fields of science
Call for proposal
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Funding SchemeERC-AG - ERC Advanced Grant
CB2 1TN Cambridge
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