Research objectives and content
This project aims to analyze the spatial and replication aspects of the regulation of beta globin gene expression and will be focused on two questions: the restoration of transcription after cell division and the spatial distribution of the globin genes in the nucleus of transgenic mice. In particular existing transgenic mice will be used to search for a mitosis 'memory protein' and the spatial distribution of the locus in mice that either contain a normal globin locus or one that is subjected to position effects. In addition a novel beta globin locus will be constructed in transgenic mice to address contacts between distant regulatory regions and the genes. At present almost nothing is known about these parameters in vertebrate cells in vivo. The beta globin locus has been studied in great detail and the existing resources in beta globin transgenic mice and novel FISH technology offer an excellent opportunity to start addressing the spatial and temporal aspect of gene regulation in mammals. Training content (objective, benefit and expected impact)
I will obtain training in homologous recombination cloning, genetic manipulation of mice, DNA and PNA based FISH technology, protein based fluorescence technology and 3D analysis technology including confocal microscopy. Links with industry / industrial relevance (22) None are foreseen at the moment.