Consequences of stress are an issue of major relevance to human health, especially its negative influences on cognition and emotion. Results suggest that the younger the individual, the more harmful are the consequences of the stress. There is considerable evidence indicating that stress experienced by a mother during pregnancy can act as a predisposing risk factor in the development of behavioural and cognitive problems at adulthood involving hyperactivity and attention deficit disorder in the offspring and increased vulnerability to develop psychiatric disorders such as depression and schizophrenia. Nevertheless, it has been observed that these disorders may not develop if the adequate postnatal stimulation is given. Research on prenatal stress (defined as the stress experienced by the pregnant mother which affects the development of the offspring) has been performed in experimental animals (mostly in altricial species like in rodents). With rodents, it is possible to study the differentiation between genetic and postnatal factors, to control the timing, intensity and duration of stress exposure and evaluate the mother-offspring interactions in a controlled environment. However, a considerable amount of neuroendocrine and neural development occurs in the rodent brain after birth, making the pups more sensitive to postnatal environmental conditions and maternal attention; this can contribute to the overall effect of prenatal stress on offspring behaviour. In contrast to this context, we decided to study prenatal stress on a precocial species, the sheep, because of their brain maturity before birth and the strong bond that develop between the ewe and her lamb which is not the case in altricial mammals. The aim of my study is to investigate the effect of prenatal stress on sheep, according to the emotional reactivity of the dams, on (1) their maternal behaviour, (2) the emotional reactivity and cognitive abilities of the young and (3) and to find possible ways to alleviate its negative consequences by the induction of positive affective experiences. In addition, the stress sensitive brain pathways associated with neural damage and neural protection will be investigated. The project is running along 3 years. Our first objective will be to select dams with extreme reactivity to stressful events in one hand and dams with very low reactivity to the other hand and to apply in both categories stressful events during the gestation. Then we will look at the maternal behaviour of the dams and how prenatal stress could interfere according to their emotional reactivity tested beforehand. Our plan is to realize cross fostering between the dams stressed during gestation and the control dams to pull apart the effects of the stress acting directly on the foetus before birth and the effects of the maternal behaviour acting on the young after birth. Emotional reactivity and judgment biases of young will be investigated. The last objective aims to subject prenatally stressed young to supposedly positive events in order to elicit positive experiences and to assess the putative therapeutic value of that behavioural strategy. In addition, the effect of prenatal stress and of positive emotion on brain morphology will be investigated in brains of the young. An originality of this project is to combine behavioural and neurological studies on the consequences of prenatal stress. This project of fundamental research will increase our knowledge on the effect of prenatal stress on emotional reactivity and cognitive abilities of individuals.

Numerous studies have shown the impacts of climate change on species distributions and extinctions, but the mechanisms through which climate variations influence individuals and populations remain poorly understood. This lack of knowledge severely hampers our ability to forecast and anticipate the effects of climate change on multitrophic relationships. The key to forecasting the effect of climate change is an understanding of the microclimate that organisms actually experience and how microclimate will be altered by global change. The project aims at determining both direction and amplitude of the climate change impacts on the population dynamics of a phytophagous spider mite feeding on apple leaves. The project will reveal the mechanisms through which climate change affects individuals and populations directly and also indirectly by altering the biotic interactions within the spider mite microclimate. The project will explore whether organisms such as insects or arachnids have the possibility to move over short distances within the local spatial scales (leaf surface, tree canopy) to buffer against extreme climatic events such as heat waves that happen at a global scale. A biophysical modelling approach will be developed as it allows to identify the precise mechanisms involved by integrating the heat budgets of the organisms. A biophysical modelling cascade will be established in order to predict the body temperature of a spider mite at a given position on a leaf surface, within the tree canopy architecture, and under a specified regional climate. This integrative approach will allow us to map favourable and risky microclimates for spider mite survival. Then, the biophysical modelling cascade will be connected to a population dynamics model to assess the consequences of spatial thermal heterogeneity in microclimates at the population scale. This framework will be used to quantify the amplitude of the micro-climatic change, and its effects on spider mite population dynamics, driven by the climate change scenarios elaborated by the IPCC. Finally, the project will lead to comprehensive predictions on the response of spider mite populations to climate change (outbreaks, local extinctions). This project is therefore at the interface between fundamental research on thermal ecology, population dynamics and applied ecology that provides policy makers and conservation biologists with tools to anticipate the negative impacts of climate change on agricultural systems.

In the past 15 years, the major effort in plant breeding has changed from quantitative to molecular genetics with emphasis on quantitative trait loci (QTL) identification and marker assisted selection (MAS). However, results have been modest. This has been due to several factors including difficulty in gene identification and long time consuming methods. GAIN-SPEED aims at demonstrating in wheat the potential of combining genomics resources, particularly the chromosome’s first draft sequence, the next generation sequencing and array technologies and association mapping to develop an original strategy to accelerate the QTL cloning. This project is proposed with a companion project, 3Bseq, submitted to the Plant Genomics call 2009, whose objective is to produce a fully annotated genomic sequence of the largest bread wheat chromosome, the chromosome 3B, anchored to genetics maps. GAIN-SPEED will draw on the sequence produced to generate molecular markers on targeted regions to speed up marker assisted selection (MAS). This marker development will be processed using Nimblegen Sequence Capture technology that enables targeted sequencing of thousands of exons or contiguous genomic loci of up to 5Mb in a single experiment. That will allow us to develop large amount of SNP markers on gene rich regions containing putative candidate genes for our traits of interest. Using the next generation of genotyping platforms, these markers will be genotyped on an association panel that will help us to select more precisely the markers associated with the traits of interest and better define the zone carrying the QTL. The most associated SNP will be the start point to screen recombinant inbred lines and generate material useful for fine mapping approach. This project doesn’t aim to map based clone QTL but it will therefore lay the foundation of faster and more efficient MAS, through the fine mapping of important QTL, bringing together fundamental research developed in the companion project and industrial interests.

The purpose of dietary assessment is to estimate intake of foods, nutrients, bioactive compounds and food contaminants for exploration of associations with health outcomes and monitoring of population nutritional status. These data are still extremely difficult to obtain, especially at the individual level, due to the wide range of foods consumed and the high heterogeneity and variability of human dietary choices. Current methods based on questionnaires and a limited number of validated biomarkers of intake available are definitely not sufficient to assess dietary intakes with the accuracy and level of detail required for modern epidemiology. Evidence has mounting that much of the inconsistency of the results in nutritional epidemiology is largely due to poor dietary assessment. This project aims at developing a new innovative and integrative approach, based on mass spectrometry metabolomics, to characterize dietary intake and nutritional status of populations. Progress in high-throughput analytical technologies and in bioinformatics now allows the simultaneous analysis of hundred(s) of low molecular weight metabolites present in biofluids or tissues and constituting the metabolome, including all metabolites directly coming from the digestion and metabolism of food components. This part of the metabolome, called the Food metabolome, encompass a huge diversity of food components that are absorbed in the gut. Any given plant food contains a few hundreds of phytochemicals from different chemical families, which when ingested with the food, are absorbed to various extent and transformed in the body by intestinal and hepatic enzymes, as well as by the microbiota, into a number of metabolites, some of them being still unidentified. Our hypothesis is that the comparison of the phytochemical part of the metabolome of individuals consuming or not a specific plant food or a F&V -rich diet should lead to the discovery of new biomarkers of intake for these foods and diets. The proposal builds on some preliminary results obtained with the Agruvasc project (ANR ALIA 2007-2009), in which we clearly discriminated urine metabolomes of subjects consuming Citrus juices, both as part of a fully controlled diet or with their regular diet. Several phytochemical metabolites reflecting citrus intake could be identified. Some were expected but most of them had not been recognized before and would have never been anticipated as putative biomarkers using a traditional approach. PhenoMeNEp will be the first attempt worldwide to search biomarkers of food intake using metabolomics in a cohort study. Two subgroups of volunteers from the SU.VI.MAX2 cohort, with contrasted level of fruit and vegetable (F&V) intake as assessed by questionnaires (1st vs 5th quintile of intake) will be selected. Plasma and urine metabolomes will be explored to identify biomarkers reflecting the consumption of F&V-rich diet or of 11 specific plant foods selected for their interest in chronic disease prevention. The metabolomic approach offers a considerable promise for dietary assessment; however progress is still hampered by several methodological problems, especially the difficulties met for annotating metabolites of phytochemicals. Primary objectives of the project will be to develop optimized MS-based analytical method and data mining workflow for the food metabolome, including a Food Metabolome database containing information on phytochemical metabolites. These developments are highly expected by the scientific community. They will make possible the full exploitation of the wealth of diet-relative information contained in the human metabolome. The project will rely on the complementary competencies from UREN (Unité de Recherche en Epidémiologie Nutritionnelle U 557 Inserm/ U 1125 Inra / CNAM /Université Paris 13) and UNH (Unité de Nutrition Humaine UMR 1019- INRA Clermont-Theix/Univ. Auvergne), regarding epidemiology, phytochemical metabolism and metabolomics.