The work is distributed in 9 different work packages (WP), each of which is taken care of by two or several partners of the network. All these work packages are based on important findings made recently by partners of the network and we expect them to be the basis for the development of new fruitful collaborations between members of the network. This goal will be reached by increasing the scientific exchanges between members of the network through regular meetings, circulation of an electronic newsletter and organisation of seminars.

Five work packages (WP) will be devoted to METABOLIC DISORDERS. A first one (WP1) will develop transgenic models to analyse and understand the role of two candidate genes (one of which is a phosphatidylinositol-5-phosphatase) in the molecular pathogenesis of type II diabetes mellitus. WP2 is devoted to the study of the role of a newly identified enzyme, fructosamine-3-kinase, in a putative deglycation pathway. The study of enzymatic deficiencies in the pathway of purine synthesis (adenylosuccinate lyase deficiency) and of L-serine synthesis, all of which result in profound mental retardation, is the subject of WP3. Congenital disorders of N-glycosylation, which lead to multisystemic diseases, often with CNS involvement, are the subject of WP4 whereas WP5 focuses on the further characterisation, and the search of protein ligands, of CFTR, the protein mutated in cystic fibrosis.

In the context of MALFORMATIONS, WP6 aims at identifying and characterising genes playing an important role in cardiac morphogenesis, vasculogenesis and angiogenesis by studying inherited human cardiac and vascular anomalies. The aim of WP7 is the structural and functional genomic analysis of a novel, evolutionary conserved imprinted domain (HSA14q, MMU12q, OAR18q) that is involved in the determination of a complex non-mendelian inheritance pattern described in sheep (polar overdominance), as well as in developmental anomalies associated with uniparental disomies in man and mice.

TUMORIGENESIS is the subject of 2 work packages. WP8, devoted to the molecular aspects of tumorigenesis in neurofibromatosis type 1, focuses on the molecular changes in Schwann cells derived from neurofibromas and malignant peripheral nerve sheath tumors from individuals with neurofibromatosis type 1. WP9 aims at the identification of novel genes involved in leukemogenesis and lymphomagenesis, the analysis of the molecular mechanisms by which these genes participate in tumorigenesis, and the evaluation of the diagnostic and prognostic relevance of the genetic aberrations.