Our research concerns mainly the pig and poultry, species studied both as livestock and as biomedical models. It is aimed at characterizing the immune response and its variability on breeding flocks, at studying the genomic regions of interest like the MHC (Major Histocompatibility Complex), and at identifying natural resistance/susceptibility to pathogens. In terms of biomedicine, the MeLiM pig is an extremely interesting model for the study of both genetic susceptilibity to the development of cutaneous melanoma and spontaneous regression of the tumors. Our partnership between INRA and the CEA (French Alternative Energies and Atomic Energy Commission) is currently based on this model.
► Genetic control of the immune response
The selection program in the chicken is based on three different criteria of the immune response and its objective is to create an original material for the study of immune response in selected lines or crossbred lines. This research includes selected and/or correlated immune responses, associations with resistance or sensitivity to infectious diseases. This material will also allow the study of selection signatures using high-throughput genotyping and the analysis of genetic testing of vaccination response (GENAVIGLU ANR program). An ongoing QTL approach with transcriptomic analyses aims at identifying genes responsible for coccidiosis resistance in the chicken (SABRE European project).
Studies on the immune response in the pig include performing phenotypic measurements of the immune response in Large White vaccinated pigs, analyzing the correlations between these phenotypes and selecting individuals with contrasted phenotypic measurements on which cell transcriptomes can be studied (IMMOPIG ANR project). The results will provide information on whether the parameters measured are genetically determined and will investigate the contribution of the transcriptome in the characterization of these phenotypes.
- Shared approaches on pig and chicken
Via our projects, we can diversify the parameters measured with the objective of characterizing the immune response in pigs and chickens. They are focused on the study of the efficiency of transfer of maternal antibodies and the analysis of the genotype of the intestinal microflora. The information obtained on the intestinal microflora will be included in the description of the phenotypes for the immune response.
Since the beginning of domestication and more recently, in particular with the production of commercial lines, livestock have been subject to a strong pressure of selection on different phenotypes, leaving an imprint on the regions that control trait variability between populations and within populations. High-throughput genotyping with SNP markers has provided access to information on the fine haplotype structure of the genome. These signatures of selection, which are very valuable to characterize biodiversity and identify causal mutations, have been sought for in chicken lines (EADGENE European Animal Disease Genomics Network of Excellence for Animal Health and Food Safety) and in Large White pig populations (IMMOPIG and DéLiSus projects).
► Genetic control of the resistance/susceptibility to melanoma
To identify the genes responsible for melanoma susceptibility in the MeLiM pig model, we have built reference families by crossbreeding MeLiM animals with healthy pigs of the Duroc breed. By tagging the genome, we have identified five QTL regions associated with melanoma. One of the QTL regions identified includes candidate genes for human melanoma some of which remain to be identified. By using the international 50 000 pangenomic SNP chip, we will be able to improve knowledge on these QTL regions.
► Study of the MHC and interesting genomic regions
- Comparative biology of the MHC: pigs, rabbits, chicken, ducks
The MHC is made up of a very polymorphic genetic system. Overall, its general organization has been conserved during evolution in vertebrates. MHC is important for three reasons: it is a major candidate locus for the individual immune response, a model region for the study of the evolution of genomes and a chromosomal segment of choice for the analysis of the concerted expression of several genes over a large distance.
From a structural point of view, we will compare the MHC in pigs, rabbits and chicken (and other birds), by integrating these data to those already available for many other vertebrate species. We study the polymorphism and expression of these genes in different experimental models to stimulate immune response and in the MeLiM model for tumor progression/regression.
- Centromeric sequences and gene coloration
The centromeric regions are poorly covered by traditional methods of genome sequencing and ongoing analyses are done in partnership with the G2B team in GABI.
Historically, coloration genes have been well studied in animal sciences since they correspond to genes with visible effects. For many years, our team has studied genes involved in coloration in the chicken and is continuing in this field with our partners. We also analyze the genes for coloration involved in the development of melanoma in the pig.
► Study of defence mechanisms
- Tumor regression in the MeLiM model
The MeLiM model presents a major interest, which is the study of spontaneous tumor regression that affects all the cutaneous tumors as well as metastases from the age of three months in piglets. It is clinically characterized by the disappearance of tumors accompanied by a depigmentation of the skin and hair. Using SSH (Suppression Subtractive Hybridization), we have characterized the molecular signature for porcine melanoma regression and we have shown that an efficient immune response exists. Currently, we are characterizing the cells present upon regression, looking for the presence of antibodies aimed at normal and tumor antigens and we will validate the role of the immune response in the induction of regression.
- Host - pathogen interactions
In the chicken, we have access to the Poultry Experimental Platform of Tours (PEAT), which houses lines that are particularly resistant to several types of pathogens (parasite/coccidiosis, virus/Marek ....) like the Fayoumi line. This type of resource is a choice model to study the genetic variability of resistance in order to find markers associated with resistance and to understand better the mechanisms of resistance.
In the pig, we have developed a transcriptomic approach to investigate host/pathogen interactions in an in vitro model of infection by the Aujeszky's disease virus in epithelial cells and immature dendritic cells.
► Resource management, production and development of genomic tools
The CRB-GADIE (National Biological Resources Centre dedicated to Livestock) is aimed at conserving and managing livestock DNA collections along with developing and providing genomics tools. Our activites depend on the species considered, on the progress made in the field of genome sequence annotation and the availability of commercial tools. The CRB-GADIE monitors technological developments on genomics tools, in particular regarding new-generation sequencing tools in transcriptomics.
► Coordination of the EADGENE Network of Excellence
Our team participates in the EADGENE network of excellence (European Animal Genomics Network of Excellence for Animal Health and Food Safety). Its objective is to structure and coordinate research in Europe on the genomics of host pathogen interactions. One of our team's scientists is the scientific coordinator.