Perhaps 40% of the coding portion of the human genome is composed of genes whose primary role is thought to be in the building of the nervous system or signaling within it. Trophic factors are amongst the most essential of the genes, as they tightly regulate the survival and plasticity of mammalian neurons. Strikingly, both the fly and the nematode lack representatives of these gene families with crucial roles in mammalian brain. In contrast, emerging evidence presented in this proposal suggests that trophic factors exist in other invertebrate phyla, as well as in early chordates; and that a multidisciplinary research program on these organisms has the potential to shed light on evolution and functionality of gene families important for complexity and regeneration of central nervous systems. The current consortium aims to address these issues by combining tools and approaches from two emerging disciplines- neurogenomics and evolutionary developmental biology.
Our main objectives are:
1. Functional genomics of secreted and surface-expressed gene products across phyla: Novel insights will ensue from characterization of the secreted and cell-surface expressed gene products in the CNS of a series of organisms of differing brain complexity. The experimental approaches will be primarily based on selective signal sequence and plasma membrane trap cloning in yeast systems, followed by large scale sequencing of the resulting libraries.
2. To obtain a comprehensive evolutionary overview of neurotrophic ligands and receptors in a wide phylogenetic range: The cloning and characterization of homologs for trk, ret, GDNF and neurotrophins across a wide phylogenetic range. Efforts will be directed to cloning and sequencing of both genomic and transcript sequences, as well as expression profiling at both mRNA and protein levels.
3. To analyze the functional roles of neurotrophic ligands and receptors in a series of model organisms: Our focus will be on the gene
Funding SchemeNET - Research network contracts
171 77 Stockholm
450 34 Fiskebaeckskil
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