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Identification and in vivo functional analysis of novel cell surface receptor-ligand pairs


Intercellular communication and adhesion are involved in many developmental processes of multicellular organisms. An increase in anatomical and physiological complexity of organisms is accompanied by an expansion of gene families encoding proteins that are involved in cell-cell recognition and signalling. Prominent examples are the members of the IgSF family, which encountered a fivefold numerical increase in vertebrates compared to invertebrates, despite the total number of genes only doubling. The identif ication of novel receptor:ligand pairs of this gene family and their in vivo functional analysis would further our knowledge of vertebrate specific developmental processes. To achieve this goal, we propose to take a genome wide approach by using the zebraf ish as a model organism. This approach will be carried out in the host laboratory of Gavin Wright at the Sanger Institute and comprises the identification of genes encoding cell surface proteins of the IgSF family (by using information from the Sanger Inst itute zebrafish genome project), the detection of novel receptor:ligand pairs among them, and the assessment of their in vivo function by means of a reverse genetic approach in zebrafish. The host institution provides an ideal scientific environment to ach ieve the mentioned objectives. The applicant will provide his expertise concerning the use of the zebrafish as a genetic model organism, whilst the host institute will provide the necessary infrastructure, equipment and expertise within in the fields of bi ochemistry and proteomics. The proposed project will therefore contribute to the exchange of knowledge between two European countries coupled to the fact that the whole genome approach to be taken is particularly suitable to establish further long-term col laborations. Ultimately, this project will help us to achieve a better mechanistic understanding at a molecular level of the processes that underlie the establishment of complex vertebrate specific features.

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