Root-knot and cyst forming nematodes are important pathogens. Nematicides were means in nematode control, but since they threatened environment and human health they were banned (EC directive 2007/619/EC). Natural plant resistance is an available and safe option, but strongly limited by the number of available genotypes and the occurrence of resistance breaking nematode populations. Furthermore, climate change positively regulates the nematode infection capacity inducing more intense infestations and greater risks to European agriculture. Therefore novel strategies must be developed. Molecular mechanisms of plant resistance to pathogens have been extensively studied and are now applied in pest management but knowledge of plant susceptibility and disease development is still limited. It is now well established that pathogens corrupt elementary plant functions and influence defence responses. Identification of plant genes which are essential for pathogens to exploit the host opens a perspective to develop new approaches to plant resistance. Members of this consortium already performed genome-wide expression profiling in Arabidopsis and tomato demonstrating that essential plant functions are manipulated during feeding site development induced by root-knot nematodes (RKN) and beet cyst nematodes (BCN). Morever, functional analysis of differentially expressed genes identify key genes essential for the development of feeding site and RKN or BCN. The NESTOR project will combine the efforts of 5 public research labs and 4 private companies to (i) discover and characterize Arabidopsis genes which are essential for disease susceptibility towards RKN and BCN and (ii) to discover target sequences in crops based on a set of genes for which an important role in feeding cell development has been shown, to generate novel resistance sources in crop plants. Orthologs of Arabidopis genes will be identified in tomato, cucumber, and sugar beet. New alleles will be generated by TILLING or Eco TILLING and tested for enhanced nematode resistance. Those with increased resistance without affecting plant development will be selected as targets. The nematology labs will first define plant susceptibility genes based on microarrays results and Arabidopsis mutant phenotyping. TILLING platforms will identify mutant lines in crops, while private companies will identify orthologues of Arabidopsis susceptibility genes in crop plant candidates and will genotype and phenotype these plants. NESTOR will increase our knowledge on plant-pathogen interactions and will generate resistance towards a large spectrum of nematode species on tomato, cucumber and sugar beet. The expected results of the project will be released to the public domain in the form of as scientific publications. They will have direct implication and application for the production of safer and healthier food by a novel approach replacing banned chemical nematicides.