Rationale
Glycogen synthase kinase-3 (GSK-3) is a naturally occurring protein in mammals that has been implicated in several diseases and also in cancer. The main purpose of this project is to study the role of this protein in the immune system.
Previous work demonstrated the use of drugs which inhibit GSK-3 to prevent tumour growth and viruses in mice. This project aims to uncover the mechanism behind these effects and identify any other proteins which may be involved. This project will advance current disease research especially in immunotherapy by using newly produced mice without the GSK-3 protein.
Plan of work and impact of our studies
The intention is to use viruses and tumours to infect mice and treat them with different drugs which inhibit GSK-3. It is thought that these drugs will decrease the virus or tumour and by analysing these animals in the lab we can determine what factors are involved in supressing the tumour or viruses. Other drugs may then be used to confirm these findings further, together with the newly produced genetically modified mice that do not contain GSK-3. These mice will enable us to ensure that the drugs being used are specific for their targets and serve as an aid towards finding any other targets which may be involved in stopping tumour growth.
Animal welfare
Mice need to be used to assess the function of these proteins in the body to test and confirm the results of previous non-animal studies. Laboratory work without mice has given rise to possible candidate parts of DNA (genes) as potential drug targets and it is essential to confirm these genes in the body and to analyse their function in tumour/virus infection and development. Any new genes identified as being of interest will be tested in non-animal based laboratory research first to determine which drug doses are suitable for further study involving animals. During mouse experiments ways to administer drugs will be examined to cause the least discomfort and pain whilst giving the desired drug response. When designing the experiments statistical analysis will be performed to ensure that the minimum number of mice will be used to give the most information. Many treated groups will often be compared against one non-treated group to reduce the number of animals used.