Davies Research Group

Research Overview

Transgenic technology enables a gene's role in development, physiology and disease to be investigated and experimentally manipulated in vivo. With this technology, models of human genetic disease can be established by introducing the equivalent human mutation into model organisms. These models can be used to investigate the underlying cause of the disease process and to trial novel therapeutic and diagnostic approaches.

The publication of the human genome sequence and recent genome-wide association studies have identified many genes and mutations whose function has not yet been ascertained, thus it is expected that the use of genetically modified models will increase dramatically over the coming years to address these challenges.

The focus of our group is to increase the efficiency and reliability of the genetic manipulation and to develop novel transgenic methodologies focused at providing in vivo analysis tools for the study of genetic variation and mutation. A further priority for the group is to reduce the animal cost of transgenic research through the generation of more predictable models.

Projects within the group are currently addressing:

the use of PhiC31 integrase enzymes for the efficient unidirectional insertion of genetic material within specific chromosomal sites.
the site specific delivery of large chromosomal transgenes
the use of alternative integrase enzymes for genetic engineering
the use of enzyme assisted DNA cleavage and recombination to facilitate genetic manipulation.

Publications

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, Bentham J, Cosgrove C, Braganca J, Cuenda A, Bamforth SD, Schneider JE, Watkins H, Keavney B, Davies B, Bhattacharya S. (2012) Functional Significance of SRJ Domain Mutations in CITED2. PLoS ONE 7(10): e46256. doi:10.1371/journal.pone.0046256

Oliver PL, Finelli MJ, Edwards B, Bitoun E, Butts DL, Becker EB, Cheeseman MT, Davies B, Davies KE. (2011) Oxr1 is essential for protection against oxidative stress-induced neurodegeneration. PLoS Genet, 7 (10), pp. e1002338.

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

Waller-Evans H, Prömel S, Langenhan T, Dixon J, Zahn D, Colledge W, Doran J, Carlton M, Davies B, Aparicio S, Grosse J, Russ A. (2010) The Orphan Adhesion-GPCR GPR126 Is Required for Embryonic Development in the Mouse. PLoS ONE 5(11): e14047. doi:10.1371/journal.pone.0014047

Funding Sources

Research within the group is currently funded by the Wellcome Trust and the British Heart Foundation

Research Area

Transgenics

Keywords

Transgenic Knock-out Functional Gene Analysis Knock-down Genetically Modified Model