Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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

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) (Hua et al., Nature 2021). 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

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.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold 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

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

2

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 (in press) (* joint corresponding)

3

Hua P, Roy N, de la Fuente J, Wang G, Thongjuea S, Clark K, Roy A, Psaila B, Ashley N, Harrington Y, Nerlov C, Watt SM, Roberts I, Davies JO, ‘Single cell analysis of bone marrow derived CD34+ cells from children with sickle cell disease and thalassemia.’ Blood 2019; 134, 2111-2115;

4

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

5

Davies JO, Oudelaar AM, Higgs DR and Hughes JR. ‘How best to identify chromosomal interactions: a comparison of approaches’, Nature Methods 2017; 14 (2), 125-134

 

Supervisors