Evolutionary neurogenomics of trophic factors

Objective

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

Fields of science

• natural sciences › biological sciences › neurobiology
• natural sciences › biological sciences › biochemistry › biomolecules › proteins
• natural sciences › biological sciences › developmental biology
• natural sciences › biological sciences › genetics › genomes

Programme(s)

• FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Topic(s)

Data not available

Call for proposal

Data not available

Funding Scheme

NET - Research network contracts

Coordinator

UPPSALA UNIVERSITY

Address

3,university Hospital
751 85 Uppsala
Sweden

Participants (7)

KAROLINSKA INSTITUTE

Sweden

Address

Retzius Vaeg 8
171 77 Stockholm

LUDWIG-MAXIMILIANS UNIVERSITY OF MUNICH

Germany

Address

Luisenstrasse 14
80333 Muenchen

ROYAL SWEDISH ACADEMY OF SCIENCES

Sweden

Address

Fiskebaeckskil
450 34 Fiskebaeckskil

UNIVERSIDAD DE LLEIDA

Spain

Address

44,avda Rovira Roure 44
25198 Lleida

UNIVERSITAT DE BARCELONA

Spain

Address

645,diagonal 645
08071 Barcelona

VRIJE UNIVERSITEIT AMSTERDAM - VERENIGING VOOR CHRISTELIJK WETENSCHAPPELIJK ONDERWIJS

Netherlands

Address

1087,de Boelelaan 1087
1081 HV Amsterdam

WEIZMANN INSTITUTE OF SCIENCE

Israel

Address

Herzel Street, 2
76100 Rehovot