Research objectives and content
The proposed scientific project is about the role of p75 both in adult neural tissue and, especially, during neural development. Together with the tyrosine kinase type receptors it is a neurotrophin receptor. Until now, however, it has been ascribed only an accessory role in signaling of the tyrosine kinase type receptors. But recently it has been shown that nerve growth factor via p75 selectively can activate specific cellular responses (apoptosis, activation of nuclear factor kB as well as of the sphingomyelin cycle). It is the aim of this proposed study to shed light on these signal transduction mechanisms. First, an attempt would be undertaken to identify potential downstream binding partners of p75. Since p75 is capable of signalling via different pathways and has been shown to harbour various conserved (intracellular) domains, the relationship between certain domains and signaling pathways would be investigated. To do so, a systematic mutational analysis of the cytoplasmic moiety of p75 would be carried out. Effects of mutations would be analyzed by various functional assays specific for the single signalling pathways.
Training content (objective, benefit and expected impact)
In the course of this project, several molecular biological techniques would be applied: especially, a yeast two-hybrid system and BIAcoreTMtechnique for identification of binding partners, and in vitro-mutagenesis for generation of mutant receptor molecules would be used.
Links with industry / industrial relevance (22)