Perspective taking, the ability to take another person's perspective, is instrumental in building successful and harmonious partnerships, from romantic relationships to international cooperation. Yet, failure to achieve perspective taking, or egocentrism, is increasingly observed in clinical and healthy populations. Fortunately, perspective taking is a skill that can be acquired through training, but, to date, existing training has only yielded limited results. This project aims to conduct the first epidemiological study of egocentrism (i.e. to assess its prevalence in Europe, its severity, its psycho-sociological determinants, and its consequences on mental health and well-being) and the first large-scale perspective-taking training intervention for both healthy and clinical populations. By distinguishing the profiles of egocentrism and identifying their key determinants, Work Package (WP) 1 will assess perspective-taking performance (and associated psycho-sociological factors) in Alzheimer, addictive disorder, anorexic, and forensic patients and in matched healthy control participantss. Building on the Supervisor’s team expertise in devising and conducting training interventions, WP2 will devise and conduct intervention programs tailored to the distinct egocentrism profiles in the same populations as WP1. WP3 will export the WP1-WP2 methodology into a free web-based assessment and training tool to conduct the epidemiological study and the large-scale training intervention in the general population, from adolescents to seniors. The assessment and training tool will be made available to all clinicians, researchers and all other actors to foster further uses such as for youth education programs, support programs for caregivers, or mental health promotion programs targeting vulnerable populations.

The aim of the MONET project (Merkel cell polyomavirus Oncogenic Network) is to provide a state-of-the-art understanding of Merkel cell carcinoma (MCC) tumorigenesis. Viral pathogens are estimated to be responsible of ~12% of cancers worldwide and represent useful models for the study of oncogenesis mechanisms. Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer detected in ~2500 patients per year in Europe and has recently been linked with a clonal integration of the Merkel Cell polyomavirus (MCPyV) in more than 80% of cases. MCPyV is a 6-protein encoding system, expressing only two proteins with reported oncogenic functions. This limited proteome size thus allows system-wide study of its associated oncogenic mechanisms. This multi-pronged project consists of: (i) identifying the critical interactions of viral and host proteins in MCC oncogenesis; and (ii), using NOD scid mice cell line derived xenografts (CDXs), validate MCPyV host-proteins drug targeting strategies to combat MCC tumorigenesis. Using cutting-edge mass spectrometry-based techniques combined with CRISPR interference approaches in relevant human cancer cell systems, these studies will uncover new protein-protein interactions essential for tumorigenesis. MCPyV+ MCC CDXs will be used to establish the functional relevance of novel virus-host protein interactions and to assess the therapeutic potential of targeting these host interactors as anti-cancer strategies. The application of these proteomic and functional approaches will allow for a better understanding of MCPyV-associated carcinogenesis. In a broader view, it will define a new framework for identifying druggable targets in pathogen-driven cancers. This project will underpin future translational researches, and hence appears as a fundamental step for therapeutic development.

Metabolic disorders such as obesity and diabetes are age-related diseases, and lead cause of death in Europe. Adiposity signals such as leptin and insulin, whose circulating levels are in proportion to body fat, convey metabolic information to neural networks that regulate energy homeostasis in the hypothalamus. In leptin-deficient humans and mice, leptin administration effectively reduces hyperphagia and obesity. Paradoxically, most cases of obesity display high circulating leptin levels that fail to reduce appetite or increase energy expenditure. This raises the possibility that leptin transport across the blood-brain barrier to the cerebrospinal fluid (CSF) or to its sites of action within the hypothalamus is a limiting step defective in obese patients. The host laboratory recently demonstrated that tanycytes, a hypothalamic glia lining the floor of the third ventricle, were responsible for shuttling leptin from the periphery to the CSF and that such conduit was blunted in mice with diet-induced obesity. Leptin transport by tanycytes could thus play a critical role in the pathophysiology of leptin resistance. The overall objective of this project is to further elucidate whether the alteration of the adiposity signals transport into the metabolic brain across hypothalamic barriers is the main cause of the onset of obesity. To this end, a combination of in vitro and in vivo approaches, using genetically modified mice and pre-clinical models of obesity, will be implemented in order to elucidate the molecular mechanisms for the transport of blood-borne leptin into the CSF by tanycytes. It is anticipated that implementation of this project will expand our knowledge of the mechanism underlying human obesity and hold therapeutic potential for treating it. Besides, the proposed project is endowed of solid formative contents that will strengthen the experience of the applicant, boosting her future scientific career and paving the way for closer scientific collaborations.