Objective
Nuclear receptors (NR) constitute a large transcription factor (TF) family with ~50 NRs identified in human or mouse. NRs have crucial roles in multiple tissues and biological processes. Consequently, misregulation of NR gene expression has been linked to several severe pathologies including cancer and neurodegenerative diseases. Despite their pathological importance, the core NR gene regulatory network (i.e. the protein-DNA interactions or PDIs controlling the expression of NR genes) has been very poorly studied. We will initiate the elucidation of the NR gene regulatory network by focusing on primary microglial cells as a non-transformed, and homogeneous model system. Microglia are poorly characterized macrophage-like brain immune cells, which may have both neurotoxic and neuroprotective properties. The majority of NRs exhibit a very dynamic expression profile in activated macrophages. Together with our preliminary data, this suggests that NRs may play a central role in microglial gene regulatory networks as well. The biological question of this proposal is to understand “which, when, and how NRs are expressed in microglia in response to neurotoxic stimuli”. We will (1) identify the temporal gene expression profiles of NRs in activated microglia; (2) identify the TFs controlling differentially expressed microglial NRs by uniquely combining two novel technologies (chromosome conformation capture and high-throughput PDI screening), whose respective co-inventors will both be involved in the project; and (3) experimentally validate the detected PDIs in microglia using siRNA and ChIP. The resulting list of high-confidence PDIs will be used to generate a first microglial NR gene regulatory network. The latter can be used for future modeling efforts to predict how the network will behave under distinct physiological conditions, or how to manipulate the network such that the neuroprotective properties of microglia are stimulated and its neurotoxic properties suppressed.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
- natural sciences biological sciences genetics chromosomes
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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.
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.
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.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2007-4-3-IRG
See other projects for this call
Funding Scheme
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.
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.
Coordinator
1015 LAUSANNE
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.