FLAMME addresses a new and emerging question, the role of the oral microbiota in the flavour perception of aroma precursors. During food consumption, oral microbes are able to generate fragrant molecules in-mouth, but evidences concerning the entailed molecular mechanisms remain scarce. FLAMME aims to identify the involved microbial enzymes and characterize their activities as a function of salivary parameters related to the host physiology, by integrating results from -omics, molecular and sensory approaches. The results will help to understand the impact of the oral microbiota metabolism on flavour perception and additionally, it will pave the way for the modulation of this metabolism for an improved control of flavour generation in-mouth.

Human infants need to apprehend much novel sensory information to rapidly engage in adaptive social communication and develop efficient social cognition. In particular, making sense of others’ faces is a challenging task for the immature infant visual system that requires experience to reach full achievement. In this context, olfaction is a functional sensory modality that conveys prior knowledge about conspecifics able to constrain the interpretation of ambiguous visual inputs. Moreover, odors are temporally and spatially stable cues that may improve the generalization of more variable face exemplars into a single category. Accordingly, the main hypothesis of the ODORINFACE project is that experience brought by olfaction during early social interactions is decisive to shape the development of face perception. Based on a pilot study showing that maternal odor enhances a face-selective response in the 4-month-old infant brain, the project will delineate the mechanisms subtending odor-driven early tuning of face perception. To meet this objective, ODORINFACE will isolate and quantify electroencephalographic (EEG) signatures of face perception in each individual infant by means of a frequency-tagging approach. Four working tasks will precisely investigate the contribution of 4 mechanisms according to 4 principles of multisensory integration: TASK 1 will determine which odor cues in maternal odor help perceive faces (intersensory redundancy); TASK 2 will evaluate whether infants’ early olfactory experience modulates face perception (developmental timing); TASK 3 will explore whether odors facilitate the perception of visual inputs as faces by improving face categorization processes (disambiguation); TASK 4 will determine the decline of the maternal odor effect over the progressive maturation of the face perception system (inverse effectiveness). ODORINFACE represents an innovative project of high feasibility which responds to basic issues on the early multisensory development of face perception in the light of a generally neglected sensory modality (i.e., olfaction). It uses an original methodological approach (i.e., frequency-tagging) to quantify EEG markers of face perception in the infant brain. Overall, this project offers new perspectives to understand and evaluate a critical function of the early social development that will undoubtedly provide numerous outcomes at both scientific and socioeconomic/societal levels, especially for clinical practices dealing with (a)typical social-cognitive development.

The process conducting to the both, orthonasal and retronasal odour perceptions includes: the biochemical odorant detection, the signal transduction and the signal integration. To detect odorant molecules, we are equipped of approximately 350 olfactory receptors that are expressed in the olfactory epithelium, and a combinatorial activation of olfactory receptors is at the basis of the generated signal. The odorant molecule triggers the olfactory receptors by crossing directly the olfactory mucus or after a salivary step. The olfactory mucus is an aqueous interface between the olfactory receptors and odorants mainly constituted of mucins and many enzymes. In mammalian, the first step of odorant detection can be modulated by the salivary and mucosal enzymatic activity. Interestingly, in human these enzymes can also be inhibited by odorants, and odorant acting as an enzyme inhibitor could modify the smell perception of another odorant. Among the enzymes, glutathione transferases (GSTs), namely, GSTA1 and GSTP1, have been identified in both, the olfactory mucus and the saliva. We assume that GSTA1 and GSTP1 may have a dual role in both, orthonasal and retronasal odorant perception. The role of GSTs in retronasal perception includes an additional salivary step compare to the orthonasal perception. During the salivary step the GSTs can modify the aromas composition, the aromas speed release and consequently their perception. The choice of these both enzymes as a model presents an additional opportunity with their polymorphism in more than 10% of the human population. The polymorphism may result in a lower GST enzyme activity, a lack of activity or a change of the molecule spectrum interacting with the GSTs. Even if the impact of the genetic polymorphism of the two olfactory GSTs on the sense of smell has not been studied yet, the link between these enzymes and human diet choice is already established. Understanding the role of these enzymes in olfaction by using a combination of different approaches, will bring crucial information on the role of these enzymes in human olfaction directly acting in the human mucosa and indirectly acting in human saliva. More particularly, OLFZYME should provide a unique opportunity (1) to characterize the binding capacity of these enzymes towards odorants, (2) to determine the impact of the polymorphism on the odorant binding, (3) to measure GSTs activity toward odorant in biological sample as saliva and mucosa, (4) to determine using cell assay and imaging and human olfactory epithelium if these enzymes are able to interact with olfactory receptors, and if yes how, (5) finally provide a proof of concept that smell perception can be modulate based on the salivary and / or olfactory mucus GSTs activity In term of societal impact, OLFZYME will allow (1) formulating food with superior sensory characteristics by rationally designing a mixture of odorants able to modulate the human smell perception; (2) to identify target populations with increased health risks due to GSTs coding genes polymorphism-induced poor diet habits. To achieve its objectives, OLFZYME proposes a multidisciplinary approach associating expertise in cell culture, protein biochemistry, imaging technics, analytical chemistry, bioinformatics and sensory analysis. Moreover, OLFZYME is a fundamental research project, which will give the opportunity to a young researcher to develop his own research thematic and lead in the future his own research group.

This project aims at determining what are the main factors and mechanisms influencing the reading emotions of others; a basic process for social adaptation. In particular, we defend the view that evaluation of self-relevance is critical for taking into account human flexibility in the reading of emotional expressions. The evaluation of self-relevance seems, at first, to vary as a function of at least four main dimensions: the specific emotional expression of the emitter, his/her direction of attention, the individual characteristics of the perceiver and the social context in which the emitter and the perceiver are interacting. By manipulating a number of these factors and by using a multi-level methodological approach of developmental psychology and social neuroscience, we propose to clarify the following issues in typical human functioning: (i) How does the reading of emotion vary as a function of self-relevant perceptual features and what underlying mechanisms mediate their bodily (facial muscles activity, autonomic activity) and subjective correlates?; (ii) How does the reading of emotion and the underlying mechanisms vary as a function of individual characteristics (gender, anxiety and empathy levels) and of social context (intimacy and group membership) ?; (iii) When and where does the evaluation of self-relevance impact neural correlates of the reading of emotion?; (iv) When does the evaluation of self-relevance during the reading of emotion emerge across development and does it influence the perceiver’s affective (liking and wanting) and cognitive processing of salient events in the environment (food and non-food cues)? This project could help identify the mechanism (s) underlying self-relevance processing during the reading of emotion and associated neural, somatic, autonomic, and behavioural outcomes. It could also offer new perspectives for assessing which basic mechanisms of the reading of emotion may be impaired in the case of clinical disorders and help to create pertinent tools for recovery.

Context. Occidental countries have to face a dramatic expansion of metabolic diseases, including obesity and diabetes, representing a major health burden in industrialized societies. The rapid increase in prevalence of these metabolic diseases is likely due to changes in environment and lifestyle, generating “obesogenic” conditions linked to an excessive energy intake. In healthy animals, food intake is permanently adjusted to fit with the cumulative energy expenditure. This remarkable energy stability is finely tuned by the central nervous system after a permanent monitoring of numerous metabolic signals within discrete brain areas. A thorough understanding of the neural mechanisms controlling food intake and metabolism will definitely help finding ways to stop the expansion of metabolic diseases. The hypothalamus, which ensures long-term stability of the inner milieu, is of major importance in the control of energy balance. Interestingly, the hypothalamus remains “plastic” in the adulthood, meaning that neuronal networks in this structure can undergo functional or morphological remodeling aimed at integrating environmental and internal conditions. Interestingly, genome-wide association studies in human have reported a strong association between high body-mass index and polymorphic loci whose genes are highly expressed in the brain and involved in neuronal plasticity. Moreover, haploinsufficiency of BDNF, a factor that mediates brain plasticity, is associated with childhood-onset obesity. These studies suggest that brain plasticity may play a role in regulating energy balance in humans. Indeed, we recently showed that plasticity of feeding circuits is required for the homeostatic regulation of food intake in mice. We identified the polysialic acid (PSA), a complex sugar modulating cell-to-cell interaction, as a mediator of the plasticity of feeding circuits. Furthermore, genetic or pharmacological removing of PSA is obesogenic. We propose to pursue our work on neural control of appetite and metabolism in mice with a powerful nutrigenomic approach to uncover molecular bases of PSA biosynthesis at the chromatin level. Objectives of the proposal and expected results. Biological explanation underlying individual predisposition to obesity and its complications are still lacking. Since PSA-dependent hypothalamic plasticity is required for homeostatic regulation of food intake, we postulate that low individual capacity of neuronal rewiring due to low hypothalamic PSA level could explain metabolic inflexibility, intolerance to dietary fat, and vulnerability to diet-induced obesity (DIO). Thus, main objectives of the project are to determine the link between hypothalamic PSA level and obesity, and to uncover molecular mechanisms underlying PSA-triggered homeostatic control of energy balance. We expect to show that low hypothalamic PSA level predisposes to DIO, and that PSA supplementation is a conceptual basis for a therapy to promote loss of weight during obesity. Next, we want to describe the chromatin-remodeling events that are crucial for PSA synthesis and for regulation of food intake. This fundamental analysis is a prerequisite allowing us to identify exhaustively all the signaling pathways activated in the hypothalamus during metabolic imbalance. We will determine whether the methylation state of St8sia4, a gene involved in polysialylation, is linked to predisposition to DIO. Methods. The team has expertise in fields of Nutrition, Metabolism and Neurosciences, and skills from behavior to molecule analysis to complete the objectives. This project relies on the use of three specific fronts of science: (i) state-of-the-art molecular biology to perform original and accurate investigation of molecular processes stimulated during a metabolic switch (i.e. in vivo chromatin immuno-precipitation, proteomic); (ii) functional exploration of energy metabolism; and (iii) gene and pharmacological manipulation in the adult hypothalamus.