Project description DEENESFRITPL Towards a better understanding of the complex brain–gut connection Some neuronal and immune cells in the intestine share anatomical features and influence each other's function, forming neuronal–immune cell units. However, whether brain-derived signals might control enteric immune functions and intestinal homeostasis has not been adequately studied. Curiously, the neurological dysfunction induced by stroke is associated with intestinal problems, including infections, inflammation and colorectal cancer. The promising preliminary data has demonstrated that stroke disrupts intestinal lymphocyte homeostasis, promoting their release from the gut to other organs. The EU-funded Neu-i-Gut project will investigate how the central nervous system affects intestinal immune homeostasis and whether brain-derived signals induce gastrointestinal disease. To that end, researchers will employ stroke and gastrointestinal disease models, together with genetic technology. Show the project objective Hide the project objective Objective Maintenance of tissue health requires a variety of cellular and molecular networks. The immune system comprises panoplies of cellsubsets that can sense endogenous and exogenous factors to ensure efficient surveillance and defense. Similarly, the nervoussystem harbors distinct neuronal populations that sense and respond to ever-changing stimuli. Interestingly, discrete neuronal andimmune cells in the intestine were shown to share anatomical confinements and influence each other’s function, forming neuronal immune cell units that act as rheostats of gut physiology. Nevertheless, whether brain-derived signals control enteric immunefunctions and intestinal homeostasis remains elusive. Importantly, neurological dysfunction induced by stroke correlates with severeintestinal problems in humans; including infections, inflammation and colon-rectal cancer.We propose to investigate how Central Nervous System (CNS) signals control intestinal immune homeostasis and how alteration ofbrain-derived signals induce gastrointestinal disease. We will explore how intestinal homeostasis and immune-mediated diseasesare regulated in the context of stroke, which is a major Public Health concern. To achieve this, we propose to employ genetic, cellularand molecular approaches to decipher how brain signals and pathways specifically shape gastro-intestinal immune homeostasis andwhat is their relevance in intestinal inflammation and cancer. To this end, stroke and gastro-intestinal disease models, together withpowerful tractable, chemogenetic technology, will be employed. Astonishing preliminary data revealed that stroke severely disruptsintestinal lymphocyte homeostasis, promoting their exodus from the gut to other organs.We foresee this project as groundbreaking, establishing the link between altered brain signals and intestinal physiology, sheddinglight into the intricate relationships between the CNS and the gastrointestinal immune system in the context of stroke, and beyond. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicineneurologystrokemedical and health sciencesbasic medicinephysiologyhomeostasismedical and health sciencesclinical medicinegastroenterology Keywords Stroke intestinal immunity DREADD colo-rectal cancer infections gut-brain axis Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD Net EU contribution € 159 815,04 Address AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD 1400-038 Lisboa Portugal See on map Region Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 159 815,04
