Transgenic technologies allow scientists to investigate the function of genes and DNA in vivo and to assess the contribution of specific genes to a particular biological process. They also allow models of human genetic disease to be established and investigated by introducing the equivalent human DNA mutation into the mouse. 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 has identified many genes whose function has not yet been ascertained and it is expected that the use of genetically modified mice will increase dramatically over the coming decades.
Despite the power of this technology, the current methodologies in use have rather significant shortcomings which make the technology rather unpredictable. Consequently, a large amount of work, financial resources and most importantly animals are used for the generation and analysis of a genetic model. Frequently this lack of predictability is due to the fact that the genetic material being added enters the DNA completely at random and can cause damage and disregulation. Additional problems are associated with the fact that certain genes may be resistant to genetic manipulation. Furthermore, many of the technologies in use are only applicable for the mouse and it would be useful for many scientists working in cardiovascular or toxicological research to develop genetically modified rat models.
The focus of our group is to increase the efficiency and reliability of transgenic technology to overcome many of these disadvantages. The ultimate aim is to reduce the animal cost of transgenic research through the generation of more predictable models.
Research within our group is focused on
- Chromosomal sites in the mouse where the insertion of genetic material can occur safely and at high efficiency
- DNA elements carrying genes which are maintained within the cells but do not integrate and disrupt the chromosome
- The use of DNA modifying enzymes to allow genetic manipulations to occur in sequences and species which have proven, up to now, resistant to genetic manipulation.