About the Project
Embryonic stem cells (ESCs) can give rise to all the cells in the body so a detailed understanding of how they commit to other cell fates is fundamentally important to understanding human development, how developmental defects arise and also potentially in therapeutic approaches using regenerative medicine. Currently we know a lot about the pluripotent state and the differentiated cell states (eg see Yang et al., 2014) but very little about how cells transition to these states. The aim of this project is to uncover novel regulators that function in this transition phase during human embryonic stem cell differentiation. We will take a novel approach based on open chromatin profiling to identify transcriptional regulators that are involved in this process (eg see Britton et al., 2017). This approach is based on the link between open chromatin regions and areas of regulatory activity such as enhancers across the genome. Genome-editing techniques based on CRISPR-Cas9 approaches will be used to test the functionality of the discovered regulators. We will couple our analysis to single cell transcriptomic and epigenetic approaches which will enable us to uncover patterns among the heterogonous behaviour of the transitional cell populations. The project will provide training in a wide range of molecular, cell biology and biochemical skills. In addition, genome-wide approaches such as RNA-seq, ChIP-seq and ATAC-seq will be used in conjunction with advanced bioinformatics analysis.
https://www.research.manchester.ac.uk/portal/andrew.d.sharrocks.html
Entry requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Funding Notes
This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships
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.
References
(1) Yang, S-H., Kalkan, T., Morissroe, C., Marks, H., Stunnenberg, H., Smith, A., and Sharrocks, A.D. (2014) Otx2 and Oct4 drive early enhancer activation during ES cell transition from naïve pluripotency. Cell Reports. 7:1968-81.doi: 10.1016/j.celrep.2014.05.037.
(2) Britton, E., Rogerson, C., Mehta, S., Li, Y., Fitzgerald, R., Ang, Y., and Sharrocks, A.D. (2017) Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma. Plos Genetics. 0.1371/journal.pgen.1006879.
Continue with Facebook
