Genetically modified models represent one of the most powerful methods of functional gene analysis. The ability to introduce specific mutations into the genome enables models of human disease to be generated, facilitating insights into the pathophysiology of disease and providing a model with which therapeutic strategies and diagnostic tools can be optimized.
The research activity of the group is focused on the development of novel methodologies for the generation of genetically modified models. The aims being to improve the reliability of the technology and to reduce the animal cost of research involving genetically modified models.
Projects within the group are currently addressing:
- the use of CRISPR/Cas9 site specific nucleases in stem cells and embryos
- the role of PRDM9 in determining the positioning of meiotic recombination events.
- integrase enzymes for the efficient unidirectional insertion of genetic material within specific chromosomal sites.
- multiplexing recombination systems for the development of multipurpose alleles
Our group provides groups within Oxford University access to transgenic technologies both on a fee-for-service type arrangement and on a collaborative basis. Technologies offered include nuclease mediated genome engineering, embryo microinjection, human iPS cell and mouse embryonic stem cell manipulation, Knock-out/-in construct design and in vivo shRNA mediated gene Knock-down. In addition, embryo rederivation and cryopreservation services are offered to facilitate the management, transfer and security of genetically modified strains.
Davies B, Brown LA, Cais O, Watson J, Clayton AJ, Chang VT, Biggs D, Preece C, Hernandez-Pliego P, Krohn J, Bhomra A, Twigg SRF, Rimmer A, Kanapin A, WGS500 Consortium, Sen A, Zaiwalla Z, McVean G, Foster R, Donnelly P, Taylor JC, Blair E, Nutt D, Aricescu AR, Greger IH, Peirson SN, Flint J, Martin HC. 2017. A point mutation in the ion conduction pore of AMPA receptor GRIA3 causes dramatically perturbed sleep patterns as well as intellectual disability. Hum Mol Genet, 26 (20), pp. 3869-3882
Hanssen LLP, Kassouf MT, Oudelaar AM, Biggs D, Preece C, Downes DJ, Gosden M, Sharpe JA, Sloane-Stanley JA, Hughes JR, Davies B, Higgs DR. 2017. Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo. Nat Cell Biol, 19 (8), pp. 952-961.
Cebrian-Serrano A, Zha S, Hanssen L, Biggs D, Preece C, Davies B. 2017. Maternal Supply of Cas9 to Zygotes Facilitates the Efficient Generation of Site-Specific Mutant Mouse Models. PLoS One, 12 (1), pp. e0169887.
Davies B, Hatton E, Altemose N, Hussin JG, Pratto F, Zhang G, Hinch AG, Moralli D, Biggs D, Diaz R, Preece C, Li R, Bitoun E, Brick K, Green CM, Camerini-Otero RD, Myers SR, Donnelly P.2016. Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. Nature 530(7589):171-6.
Dolatshad G, Biggs, D, Diaz R, Hortin N, Preece C, Davies B. 2015. A versatile transgenic allele for mouse overexpression studies Mammalian Genome, 26(11-12):598-608
Zeron-Medina J, Wang X, Repapi E, Campbell MR, Su D, Castro-Giner F, Davies B, Peterse EF, Sacilotto N, Walker GJ, Terzian T, Tomlinson IP, Box NF, Meinshausen N, De Val S, Bell DA, Bond GL. 2013. A Polymorphic p53 Response Element in KIT Ligand Influences Cancer Risk and Has Undergone Natural Selection. Cell, 155 (2), pp. 410-422.
Xu Z, Thomas L, Davies B, Chalmers R, Smith M and Brown W. 2013. Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome. BMC Biotechnology 13 (87), doi:10.1186/1472-6750-13-87
Davies B, Davies G, Preece C, Puliyadi R, Szumska D, et al. (2013) Site Specific Mutation of the Zic2 Locus by Microinjection of TALEN mRNA in Mouse CD1, C3H and C57BL/6J Oocytes. PLoS ONE 8(3): e60216. doi:10.1371/journal.pone.0060216
Chen C-m, Krohn J, Bhattacharya S, Davies B. (2011) A Comparison of Exogenous Promoter Activity at the ROSA26 Locus Using a PhiC31 Integrase Mediated Cassette Exchange Approach in Mouse ES Cells. PLoS ONE 6(8): e23376. doi:10.1371/journal.pone.0023376
Research within the group is currently funded by the Wellcome Trust and the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs)
Genome editing, Site-specific nuclease, Transgenic, Knock-out, Functional Gene Analysis, Knock-down, Genetically Modified Model, CRISPR-Cas9