Project description
Investigating the role of postnatal epithelial cells in human health after early pathogen exposure
The enteric microbiota, the mucosal immune system and the epithelial barrier are the factors that establish intestinal host–microbe homeostasis after birth. The mucosal immune system and the establishment of the enteric microbiota have been extensively studied in contrast to the postnatal evolvement of epithelial cells. The EU-funded EarlyLife project aims to generate a comprehensive map of postnatal epithelial cell type differentiation and investigate the impact of early life infection by important human bacterial, viral and parasitic pathogens on long-term immune-mediated, inflammatory and metabolic diseases. These long-term effects will be functionally studied using epigenetic and transcriptomic profiling, microbiota-transfer experiments and human stem cell organoid cultures in combination with in vivo genetic models.
Objective
Infections of the gastrointestinal tract and their long-term consequences remain a major cause of childhood mortality and morbidity worldwide. In addition, early life is recognized as a critical and non-redundant time period to prime the mucosal tissue and establish the enteric microbiota that determine the risk to develop prevalent inflammatory, immune-mediated, and metabolic diseases. Three factors: the enteric microbiota, the mucosal immune system and the epithelial barrier cooperate to establish intestinal host-microbial homeostasis after birth. Maturation of the mucosal immune system and establishment of the enteric microbiota have been extensively studied. In contrast, postnatal evolvement of epithelial cell type heterogeneity and functional specialization and the influence of enteric infection on this process have not been explored. With EarlyLife, I propose to further advance innovative, multiscale technical approaches and analytical protocols in combination with novel in vivo models to generate the first comprehensive map of postnatal epithelial cell type and subtype differentiation and analyze the impact of early life infection by important human bacterial, viral and parasitic pathogens. Long-term inflammatory, immune-mediated and metabolic effects will be functionally studied using epigenetic profiling, microbiota-transfer experiments, stem cell organoid culture and co-culture, as well as genetic models. Identified mechanisms will be confirmed using single-cell analysis of human mucosal biopsies, human stem cell organoids and transcriptomic profiling of human fecal samples. As a result, I expect to identify mechanisms of enhanced infection susceptibility of the neonate, decipher the critical and non-redundant influence of the postnatal period for mucosal homeostasis and explain the role of early life imprinting for long-term immune-mediated, inflammatory and metabolic diseases.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- social sciences sociology demography mortality
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-ADG - Advanced Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2020-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
52074 Aachen
Germany
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