Investigating the processes and mechanisms of cellular decision-making

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This project aims to investigate the processes and mechanisms of cellular decision-making in the context of mammalian development, with a focus on the first decision that cells make in the embryo - between neuroectodermal and mesodermal fates. This decision can be modelled in mouse embryonic stem cells (mESCs) which open a number of experimental and theoretical avenues that provide a suitable substrate for exploring this decision. The primary approach will be to capitalise on the recent developments in single-cell technologies by analysing single-cell RNA-seq data in order to explore and describe the underlying genetic programs. There are several goals within this project: (1) Investigate publically-available sources of data and collate the data into a single database to enable meta-analysis, where possible (2) Identify whether the neuroectodermal fate can be considered 'primary', that is there a 'transcriptomic signature' of neural fate present in cells before the decision to differentiate. This will be considered in the context of 'fate races' as described in Rue & Martinez Arias, 2015.(3) Investigate extensions of the 'quasi-potential landscape' framework to conceptualise and describe the behaviour of the complex pluripotency and differentiation circuits implicated in this decision.(4) Generate data of the mesodermal differentiation trajectory if, after initial analysis, it is deemed necessary.There has been a great deal of success in using single cell transcriptomic methods to detect and characterise populations of cells; however. there has been less progress in the investigation of functional properties underlying a cell's expression profile.