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Content archived on 2024-05-30

Large-scale integrative biology of human dendritic cells

Objective

The immune system is composed of different cell types that work in a coordinated manner to maintain the integrity of the organism in situations of threats or danger. Dendritic cells (DC) act as sentinels in peripheral tissue and mucosal interfaces where they integrate a diversity of danger- and inflammation-associated stimuli, then migrate to secondary lymphoid organs, and instruct naïve CD4 T cells to differentiate into the appropriate effector T cells. Hence, they play a critical role in linking innate to adaptive immunity. Three important levels of complexity characterize the DC system: 1) DC integrate multiple stimuli within complex inflammatory microenvironments, 2) these signals induce a complex output response and modify the global state of DC (environmental plasticity), 3) DC exist in different subsets generated by distinct differentiation pathways (evolutionary selection). In this proposal, we use cellular and molecular immunology combined to computational biology and modeling to study these properties at the large-scale level, and understand their interdependence in controlling DC biology. We ask the following specific questions: WP1: How DC subsets integrate combinations of stimuli at the large-scale level; WP2: How single and multiple stimuli modify DC state over time (dynamic modeling); WP3: How the DC global state influences response to a given stimulus. These questions will be addressed using a data-driven strategy combining global unsupervised exploratory analysis, gene-by-gene analysis and modeling, experimental validation of testable hypothesis. Through this systems level integrative approach, we will dissect the complexity of DC reciprocal interactions with their complex microenvironment, and hope to unravel novel mechanisms and concepts determining DC function.

Fields of science (EuroSciVoc)

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Topic(s)

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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2011-StG_20101109
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Funding Scheme

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ERC-SG - ERC Starting Grant

Host institution

INSTITUT CURIE
EU contribution
€ 1 498 996,80
Address
RUE D ULM 26
75231 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

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Beneficiaries (1)

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