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Novel chromatin opening elements for stable gene expression

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  • Full or part time
    Dr West
  • Application Deadline
    No more applications being accepted
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Recombinant genes are typically silenced when integrated into the genome of mammalian cells as most of the genome is repressive to transcription at any given time. This represents a major bottleneck to experimental biology, the manufacture of biopharmaceuticals, and also limits the efficacy of gene therapies. DNA sequence elements with dominant chromatin opening activity can be used to overcome this substantial problem. We have recently developed a sophisticated high throughput assay platform that allows the functional characterisation of novel elements at pre-defined chromosomal locations. You could study novel chromatin opening elements using this assay and combine this approach with our established CRISPR genome and epigenome editing technologies. You would study the epigenetic mechanisms employed by chromatin opening elements and work with our industrial collaborators to establish their utility in biotechnological applications. A placement at our industrial collaborator’s research facility may be available. The project will both provide fundamental insight into the DNA elements that organise mammalian genomes and deliver powerful new tools for biotechnology and gene therapy applications.

The West research group is home to bright and highly motivated researchers interested in all that is chromatin, epigenetics and CRISPR. We employ a wide range of chromatin, genomic and epigenomic techniques to address fundamental aspects of gene regulation during vertebrate development and human disease. We are located in the state-of-the-art Wolfson Wohl Cancer Research Centre, home of the Institute of Cancer Sciences and world class ’omics facilities.

When applying, please search for the project using ’novel chromatin’ in the programme description box and select the full title as it appears underneath.

Recommended start date is 1 October although this is flexible.

Funding Notes

This project is for self-funded students who have secured their own scholarships. Provide details of your scholarship on application. Contact the supervisor in the first instance.

References

Publications arising from previous postgraduate research students in the group are listed below.
1. Barkess, G., and West, A. G. (2012) Chromatin insulator elements: establishing barriers to set heterochromatin boundaries. Epigenomics, 4 (1). pp. 67-80. (doi:10.2217/epi.11.112)
2. Zhou, Y., Kurukuti, S., Saffrey, P., Vukovic, M., Michie, A.M., Strogantsev, R., West, A.G., and Vetrie, D. (2013) Chromatin looping defines expression of TAL1, its flanking genes, and regulation in T-ALL. Blood, 122 (26). pp. 4199-4209. (doi:10.1182/blood-2013-02-483875)
3. Baxter, E.W. et al. (2013) The inducible tissue-specific expression of the human IL-3/GM-CSF locus is controlled by a complex array of developmentally regulated enhancers. Journal of Immunology, 189 (9). pp. 4459-4469. (doi:10.4049/jimmunol.1201915)
4. Ma, M.K.-W., Heath, C., Hair, A., and West, A. (2011) Histone crosstalk directed by H2B ubiquitination is required for chromatin boundary integrity. PLoS Genetics, 7 (7). e1002175. ISSN 1553-7390 (doi:10.1371/journal.pgen.1002175)
5. Dickson, J., Gowher, H., Strogantsev, R., Gaszner, M., Hair, A., Felsenfeld, G., and West, A. G. (2010) VEZF1 elements mediate protection from DNA methylation. PLoS Genetics, 6 (1). e1000804. (doi:10.1371/journal.pgen.1000804)

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