About the Project
However, exactly how does the transcriptional machinery interpret oscillatory transcription factor dynamics is in fact completely unknown. How do the oscillatory protein dynamics interface with the evidence of bursty stochastic mRNA expression?
To gain insight into these questions, we propose to simultaneously monitor with live imaging the oscillatory dynamics of a transcription factor, neurogenin, and the transcriptional response of a downstream target neuroD. Both will be assayed by live imaging, in real time. We already have a neurogenin labelled protein that can be used for live imaging of the protein dynamics and during this project we will make an endogenous reporter of the neuroD transcription using the MS2 system.
Our work will be carried out in neural stem cells. The student will learn tissue culture, differentiation protocols for neural stem cells, CRISPR/Cas9 genome editing technology and confocal imaging/analysis.
Candidates are expected to hold (or be about to obtain) a first class degree (or equivalent) in Molecular/Cellular/Developmental Biology. Candidates with experience in molecular biology lab projects are encouraged to apply.
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
Quantitative single-cell live imaging links HES5 dynamics with cell-state and fate in murine neurogenesis.
Nat Commun. Jun 27;10(1):2835. doi: 10.1038/s41467-019-10734-8.
Vera M1, Tutucci E2, Singer RH3, 2019.Imaging Single mRNA Molecules in Mammalian Cells Using an Optimized MS2-MCP System. Methods Mol Biol. 2019;2038:3-20. doi: 10.1007/978-1-4939-9674-2_1.
Deignan, L., Pinheiro, M.T., Sutcliffe, C., Saunders, A., Wilcockson, S.G., Zeef, L.A.H., Donaldson, I.J. and Ashe, H.L. (2016). Regulation of the Dpp signaling-responsive transcriptional network in the Drosophila embryo. PLOS Genetics 12, e1006164. PMCID: PMC4933369
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