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Development of novel CRISPR strategies for targeted gene therapies

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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

Recent advances in genomics and epigenomics are uncovering the determinants of a wide variety of genetic and epigenetic disorders. Coupled with the rapid progress of stem cell biology, there are many opportunities for novel and powerful genetic therapies using a patient’s own cells. Classical approaches of transgene delivery, often using viral vectors, encounter a number of problems such as the efficiency of gene delivery, chromosomal silencing and insertional mutagenesis. Powerful CRISPR technology has been used by many groups to perform accurate gene correction in patient stem cells or induced pluripotent cells. This is an exciting step, but these methods are very inefficient and require time consuming isolation and characterisation of corrected cells. We have devised novel genetic insertion methodologies that use CRISPR for highly efficient gene correction. Initial experiments using these methodologies look promising. You could develop and apply our methods to develop gene correction strategies for common genetic diseases. You would work in mammalian cell lines and stem cells and would focus on the efficiency and accuracy of your strategy and then the performance of the corrected gene locus. We collaborate with several groups that are developing gene correction strategies for blood and neurological disorders. Your work would also have impact on our industrial biotechnology projects.

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 the word ’CRISPR’ in the programme description box and select the full programme title which will appear 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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