Postdoctoral Research Scientist
DNA methylation patterns are reprogrammed genome-wide in early development and this is followed by rapid de novo methylation at the exit from pluripotency and leading up to gastrulation. It is thought that lineage and cell fate specific methylation patterns are established at these critical stages. We are profiling DNA methylation and transcription patterns across these priming and differentiation stages both in in vitro cell systems and in vivo in mouse embryos. We have detected profound heterogeneity of methylation and transcription patterns prior to cell fate decisions, leading to the hypothesis that such ‘noise’ may facilitate fate decisions. Later in development we found that active tissue-specific enhancers are marked by specific DNA modifications (5fC), and that 5fC at intron-exon boundaries may be involved in the regulation of splicing.
The successful candidate will work with already established mutant cell or mouse lines, and will additionally use CRISPR technology to engineer new cell lines with deletions of critical factors for the regulation of DNA modifications. The candidate will characterise the mutant cells or embryos using single cell transcriptional approaches (scRNA-seq, scBS-seq, scM&T-seq) and low cell number epigenetic assays (ChIP-seq; 5fC-seq) to define levels of epigenetic and transcriptional noise, and splicing patterns. To functionally associate the DNA modification dependent changes with altered lineage priming or differentiation, the candidate will carry out in vitro differentiation assays or test cell lines for differentiation in chimeras in vivo. The work on splicing may involve manipulating epigenetic marks and their readers in cell lines.
We are looking for an experienced and highly motivated postdoctoral scientist to lead this research project. The successful candidate will have demonstrated experience in molecular biology including the preparation of RNA-seq, BS-seq, or ChIP-seq libraries, and an extensive knowledge of epigenetics, transcriptional regulation, developmental biology, or stem cell research. Previous experience with low cell number epigenetic and transcriptional or Crispr/Cas techniques is highly desirable.
Funding for this position is available for up to 18 months.
Some recent references can be found below. For more information on our science please visit our website http://www.babraham.ac.uk/our-research/epigenetics
Von Meyenn, Iurlaro, Habibi et al 2016 Molecular Cell, von Meyenn et al 2016 Dev Cell, Branco et al 2016 Dev Cell, Angermueller, Clark, Lee, Macaulay et al 2016 Nature Methods.
Full details of the position can be found here.
On applying please quote reference WR-PD-LTC
Starting salary is £30,751 per annum to £34,166 per annum depending on experience.
Closing date for completed applications is Tuesday 04 April 2017.
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