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About the Project

My lab is interested in understanding how the genome functions and leveraging this to develop genome editing strategies to treat human disease.

In higher eukaryotes many genes are controlled by regulatory elements called enhancers, which are often located hundreds of thousands of base pairs distant from the gene. Enhancers contain small sequences (~10bp) which bind transcription factors and these make physical contact with the proteins at the promoter to activate gene expression. Until recently, we have had limited ability to define the detail of physical contacts that control genes below 1kb resolution.

We have recently developed a new method (Micro Capture-C) to define genome architecture in unprecedented detail (down to base pair resolution). We are using the new technique to study the fundamental mechanisms of gene regulation and to define how variation in genome sequence links to human disease. These assays are very challenging to analyse and we have developed novel computational approaches for interrogating these data sets.

The lab also has expertise in cutting edge genome editing technology. As a haematologist with a specialist interest in bone marrow transplantation and cellular therapy, I am keen to develop novel clinical genome editing approaches. At present, we are working with biotech to bring a genome editing approach we have invented for treating thalassaemia and sickle cell disease into the clinic.
The lab specialises in combining wet lab approaches with computational biology and we have a number of exciting projects in both functional genomics and clinical genome editing. We are very keen to take on new students and are happy to try to tailor projects to the individual students interests.

Training Opportunities
The lab provides training in the following areas:
1. Advanced genome editing, using conventional CRISPR and more recent developments including base editing and prime editing using different approaches (RNP, mRNA and Plasmid)
2. Cloning
3. Epigenetics methods (ATAC, ChIP and Chromosome Conformation Capture (3C))
4. Development of novel high throughput sequencing methods
5. Cell biology including flow cytometry and single cell methods
6. Bioinformatics and computational biology (we have expertise in developing novel methods of data analysis, particularly for 3C methods)


Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division’s Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Funding Notes

Funding for this project is available to scientists through the WIMM Prize Studentship and the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.

For October 2021 entry, the application deadline is 8th January 2021 at 12 noon midday, UK time.

Please visit our website for more information on how to apply.

References

Peng Hua, Noemi Roy, Josu de la Fuente, Guanlin Wang, Supat Thongjuea, Kevin Clark, Anindita Roy, Bethan Psaila, Neil Ashley, Yvonne Harrington, Claus Nerlov, Suzanne M Watt, Irene Roberts, James O J Davies, ‘Single cell analysis of bone marrow derived CD34+ cells from children with sickle cell disease and thalassemia.’ Blood 2019; 134, 2111-2115;

A Marieke Oudelaar, James O J Davies, Lars LP Hanssen, Jelena M Telenius, Ron Schwessinger, Yu Liu, Jill M Brown, Damien J Downes, Andrea M Chiariello, Simona Bianco, Mario Nicodemi, Veronica J Buckle, Job Dekker, Douglas R Higgs, Jim R Hughes ‘Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains’ Nature Genetics 2018; 50, 1744-55

Mohsin Badat, Douglas Higgs, James Davies ‘Editing of Haemoglobin Genes’ UK Priority Application (2018) WO2020065303A1 PCT/GB2019/052696

Davies J.O.J., Oudelaar A.M., Higgs D.R. and Hughes J.R. ‘How best to identify chromosomal interactions: a comparison of approaches’, Nature Methods 2017; 14 (2), 125-134

Davies J.O.J., Telenius J.M., McGowan S., Roberts N.A., Taylor S., Higgs D.R. and Hughes J.R. ‘Multiplexed analysis of chromosome conformation at vastly improved sensitivity’, Nature Methods 2016; 13, 74-80

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