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Research Associate at Imperial College London

A postdoc position is available at Imperial College London. Citizens of any country are eligible to apply. The deadline for applying is September 23, 2018.

The "Regulatory Network Dynamics and Cell Identity" group (https://lms.mrc.ac.uk/research-group/regulatory-dynamics-and-cell-identity/ ), headed by Dr Nicola Festuccia, aims at combining synthetic biology, new strategies for genome editing and high-throughput screening techniques to understand how transcription factors (TFs) cooperate to control the activity of the cis-regulatory elements (REs). In particular we aim at understanding how TF binding and function is responding to cell-cycle progression, and how these changes might influence the rearrangement of gene regulatory networks during cell fate transitions.

We will use murine Embryonic Stem Cells (ESC), and the network of TFs that sustains their pluripotent identity, as a model to address these unanswered aspects of gene regulation. We previously identified a pluripotency TF, Esrrb, which remains bound to the chromatin during mitosis, a process known as bookmarking. We were recently able to show that Esrrb binding prevents the loss of chromatin organisation at REs during division, possibly facilitating the re-establishment of binding by other TFs in the following cell cycle. Yet the kinetics and mechanisms through which functional complexes of TF are formed at REs after the chromatin decondenses remains unexplored. We will address this question in self-renewing ES cells and explore how mitotic TF binding might influence these processes. We will then explore how loss of Esrrb during the conversion of nave into primed pluripotency, impacts the robustness and kinetics of RE reactivation. We aim at understand whether decommissioning or maintenance of REs is decided soon after cell division.

Within the frame of this project, the group is now inviting applications for a post-doctoral researcher with wet-lab experience and a solid conceptual background in the fields of chromatin biology, transcription and epigenetics. The candidate will be tasked with:
- Identifying novel bookmarking factors, both in nave and primed pluripotent cells, and characterising their importance in sustaining cell identity.
- Preparing custom ChIP-seq, MNase-seq and ATAC-seq libraries to analyse the effects of bookmarking on endogenous RE reactivation after division, in nave ESC and at different times during the conversion to primed pluripotency.
- Using genome editing to generate synthetic REs displaying different configurations of binding sites for bookmarking and non-bookmarking TFs. By developing novel readout methods based on next-generation sequencing, the candidate will explore how the DNA sequence determines TF binding in mitosis, and impact on the re-establishment of occupancy in G1.
- Construct knock-in reporters of enhancer activity based on live imaging of transcription. The candidate will then employ these reporter lines to monitor RE re-activation after mitosis, in self-renewing cells and during early differentiation.

The appointed candidates will be encouraged and assisted in applying for independent funding: at least a first-author publication from previous work is therefore recommended. The selected researcher will be expected to supervise Masters and PhD students, building a track record of successful mentoring. Candidates are expected to be highly passionate and motivated, flexible in their commitment, collaborative and have good written and oral communication skills in English. The successful candidates will enjoy working with passionate fellow researchers, in an intellectually stimulating environment, where open discussion, exchange of ideas and creativity are considered as the basis of scientific research.

For informal inquiries or questions please contact Dr Nicola Festuccia directly (nicola.festuccia@lms.mrc.ac.uk).

Should you have queries about applying for the role, please contact: recruitment@imperial.ac.uk


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