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  • James Davies

ABOUT THE RESEARCH 

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 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. We have previously licensed an approach for treating thalassaemia and sickle cell disease to BEAM therapeutics. 

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.

Please see the Weatherall Institute for Molecular Medicine (WIMM) for information about applications for a DPhil in Medical Sciences with groups based in the WIMM.

 

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.

 

PUBLICATIONS

1

Badat M, Ejaz A, Hua P, Rice S, Zhang W, Hentges LD, Fisher CA, Denny N, SchwessingerR, Yasara N, Roy NBA, Issa F, Roy A, Telfer P, Hughes J, Mettananda S, Higgs DR and Davies JO ‘Direct correction of haemoglobin E β-thalassaemia using base editors’ Nature Communications 2023 14, 2238

2

Hamley JC, Li H, Denny N, Downes D and Davies JO ‘Determining chromatin architecture with Micro Capture-C’ Nature Protocols 2023 

3

Aljahani A, Hua P, Karpinska MA, Quililan K, Davies JO* Oudelaar AM* ‘Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF’ Nature Communications 2022 13:1-13 (* joint corresponding)

4

Downes DJ, Cross AR, Hua P, Roberts N, Schwessinger R, Cutler AJ, Munis AM, Brown J, Mielczarek O, de Andrea CE, COMBAT Consortium, Gill DR, Hyde SC, Knight JC, Todd JA, Sansom SN, Issa F, Davies JO* and Hughes JR* ‘Identification of LZTFL1 as the likely effector gene at a severe COVID-19 risk locus.’ Nature Genetics 2021 53:1606–1615

5

Hua P, Badat M, Hanssen LLP, Hentges LD, Crump N, Downes DJ, Jeziorska DM, Oudelaar AM, Schwessinger R, Taylor S, Milne TA, Hughes JR, Higgs DR and Davies JO ‘Defining genome architecture at base pair resolution’ Nature 2021; 595(7865):125-129