Research objectives and content
The studies of transcriptional activation in response to interferons have uncovered a novel signal transduction pathway from cell surface receptors to the nucleus. The intracellular signalling events are mediated by two novel families of effectors: the JAK family of tyrosine kinases and the STAT family of transcription factors. The JAK/ STAT pathway was found to be activated by a wide range of cytokines and growth factors. The ubiquitous participation of JAKs and STATs in cytokine and growth factor signalling strongly implies that variants of the proteins and differences in their celluar production levels are associated with diseases or with improved disease resistance. Genomic and cDNA clones of various JAK and STAT proteins of farm animal species (swine, cattle, sheep, rabbit) will be cloned and automatically sequenced. The JAK and STAT clones of farm animal species will be functionally assayed with respect to their ability to genetically complement human cell lines defective in the JAK or STAT proteins. The sequence information obtained will be used to screen these species for polymorphisms in the coding region of the genes as well as in the 5` and 3` regulatory sequences and to isolate JAK/ STAT variants. This will give insight in the evolutionary conservation of these proteins and will help to identify domains wich are important for structure/ function. In addition the data will used to assess the potential impact of JAK/ STAT variants on health traits of farm animals.
Training content (objective, benefit and expected impact)
The training content will include basic molecular genetic techniques. In addition I will gain experience in the handling and and programming of an automated laboratory workstation and of various automated sequencing techniques (single and multicolor gelelectrophoretic sequencing, capillary sequencing.
Links with industry / industrial relevance (22)