Job Description Postdoctoral Research Scientist (PRG-PD-BB) Length of appointment Three years in the first instance

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1 Job Description Postdoctoral Research Scientist (PRG-PD-BB) Department Epigenetics Grade BI 6 Salary range 30,751 to 34,166 per annum Length of appointment Three years in the first instance Location Babraham Institute Working Hours 37 Job Profile Summary The successful candidate will work with already established EZH2-deficient cell lines, and will additionally use CRISPR technology to engineer new cell lines with further Polycomb gene deletions. The post holder will characterise the mutant cells using single cell approaches (scrna-seq; Fluidigm RT-qPCR; CyTOF) and low cell number epigenetic assays (ChIP-seq; ATAC-seq) to define the level of epigenetic and transcriptional heterogeneity. To functionally associate the EZH2-dependent transcriptional changes with altered lineage priming, the post holder will flow sort lineage-primed cell populations and subject the isolated populations to self-renewal and directed differentiation assays. The overall significance of this work will be to characterise the molecular basis for multi-lineage priming in human pluripotent stem cells. The successful candidate will have demonstrated experience in molecular biology including the preparation of RNA-seq and ChIP-seq libraries, and an extensive knowledge of stem cell biology and epigenetic research. Previous experience with low cell number epigenetic and transcriptional techniques is highly desirable. Polycomb-group proteins and their associated repressive histone mark H3K27me3 modulate the transcription of lineage-determining factors. We have discovered that the deletion of the Polycomb-group protein EZH2 in human pluripotent stem cells leads to their compromised self-renewal and to the derepression of Polycomb-group target genes including a large number of developmental factors (Collinson et al., 2016). We would now like to investigate whether the loss of EZH2 alters the epigenetic and transcriptional heterogeneity within the cell population and also to characterise the impact on lineage priming in human pluripotent stem cells. Our hypothesis is that EZH2 endows human pluripotent stem cells with the flexibility to transiently explore different primed states, and that the loss of EZH2 perturbs this flexibility and leads to more restrictive lineage priming.

2 Key areas of Responsibility Design, implementation and interpretation of own experiments Method development Work with line manager to decide direction of project Work with colleagues on related or collaborative projects Mentor junior staff/students Present results at lab meetings, Institute meetings and conferences Write drafts of manuscripts, together with the line manager For more information on the work of the group, please visit: Recommended readings Collinson A, et al. Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self- Renewal and Differentiation Defects in Human Embryonic Stem Cells. Cell Reports (10): PMID: Collier AJ, et al. Comprehensive Cell Surface Protein Profiling Identifies Specific Markers of Human Naive and Primed Pluripotent States. Cell Stem Cell (6): PMID: Freire-Pritchett P, et al. Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells. Elife pii: e PMID: Vallot C, et al. XACT Noncoding RNA Competes with XIST in the Control of X Chromosome Activity during Human Early Development. Cell Stem Cell (1): PMID: Novo CL, et al. The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells. Genes Dev (9): PMID: April 2016

3 Person Specification Criteria Education & Qualifications PhD in developmental biology, molecular biology, genetics or related biological discipline Essential () Highly Desirable () Desirable () Shortlisting (please indicate the specific criterion that can be shortlisted) () Relevant Experience Expertise in molecular biology Hands on experience with making RNA-seq and ChIP-seq libraries First or second author research publication or preprint within the past two years (time for career breaks will be taken into consideration) Experience in low cell number techniques (scrna-seq, scatac-seq, scbs-seq) Stem cell culture and their manipulation (preferably human ES/iPS cells) Knowledge & Skills Knowledge of epigenetics and stem cell biology Ability to bioinformatically analyse ChIP-seq and RNA-seq datasets An aptitude for the development and troubleshooting of molecular methods Able to comprehend and communicate in the English language to a level appropriate for the position Proactive, motivated and uses initiative to move projects forward Excellent interpersonal skills with the ability to communicate with staff at all levels Ability to work independently and as part of a team Excellent accuracy and attention to detail Excellent organisational skills, with good time management Strong IT skills, including Microsoft Office

4 Personal Attributes & Characteristics Willing to work with human embryonic stem cells Self-motivated and adaptable to change Willing to work flexibly at times Empathy with the life sciences work of the Institute April 2016

5 The Babraham Institute Postdoctoral Research Scientist (PRG-PD-BB) INFORMATION ON TERMS & BENEFITS The following is for information only and is not contractual statement of terms and conditions. Holiday Entitlement Bank Holidays Christmas Closure days Pension Scheme 25 days per annum Applicable to England and Wales 3 days Babraham Institute is able to offer membership of a Group Personal Pension Scheme. We will provide you with details of this scheme once you commence work. Membership of the scheme is not compulsory but it is designated as Babraham Institute s Stakeholder exempt plan. The Institute does not make contributions to other personal pension schemes. Restaurant Facilities Onsite Accommodation Social There are a number of facilities on site. The Institute has a number of hostels, flats and houses which can be rented. (There is currently a waiting list for all types of accommodation.) Sports & Social Club Nursery Nursery and Holidays Playscheme on site. (Availability of places is dependent on demand.) Car Parking There is free car parking in the Institute Car Park. The Institute is committed to the implementation of a commuting strategy to try and reduce the growth in numbers of cars used to travel to work Any offer of employment will be subject to security screening and may be subject to health screening. Any offer may also be subject to a general medical