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Revealing molecular mechanisms of gene silencing


About This PhD Project

Project Description

Regulation of transcription through chromatin architecture is governed by nucleosome remodelers and chromatin modifying complexes. These macromolecular machines are essential for establishing the transcriptional programs of eukaryotic cells, which underpin survival, cellular identity and many disease states. We aim to understand the mechanisms that silence genomic regions and use the powerful yeast model system S. pombe to study the histone H3K9 methyltransferase complex CLRC and the nucleosome remodelling and deacetylation complex SHREC. We have established architectural principles of the SHREC complex (Job et al., 2016) and have shown how its nucleosome remodelling subunit is recruited by a member of the HP1 family (Leopold and Schalch, 2018). Using a comprehensive structure-function approach you will be involved in revealing how SHREC or CLRC engage with chromatin to silence genes. You will learn both structural biology (emphasis on Cryo-EM, but X-ray crystallography and NMR are also available) to understand how the molecules perform their function and will use genetic manipulation of the same molecules in yeast to establish a comprehensive view of the molecular mechanism by monitoring genome structure and gene expression (nucleosome mapping, chromatin immunoprecipitation (ChIP) and measuring transcript levels by quantitative PCR).

Eligibility:
UK/EU applicants only.

Entry requirements:
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.
The University of Leicester English language requirements apply where applicable: https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

How to apply:
Please refer carefully to the application guidance and apply using the online application link at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

Project / Funding Enquiries:
Application enquiries to
Closing date for applications: Sunday 12th January 2020

References

Job, G., Brugger, C., Xu, T., Lowe, B.R., Pfister, Y., Qu, C., Shanker, S., Baños Sanz, J.I., Partridge, J.F., and Schalch, T. (2016). SHREC Silences Heterochromatin via Distinct Remodeling and Deacetylation Modules. Mol. Cell 62, 207–221.

Leopold, K., and Schalch, T. (2018). Dedicated interaction between HP1 protein Chp2 and remodeling factor Mit1 regulates heterochromatin. Submitted.

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