Project description
Molecular mechanisms of glucocorticoid receptor-mediated immunomodulation
Glucocorticoids, such as cortisol, act through two receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), and they mediate the effects of the stress hormone cortisol. Until recently, the research on cortisol action had mainly focussed on the function of the GR and less on that of the MR. The main goal of the EU-funded MeRGeR project is to uncover the role of the MR in mediating the effects of cortisol on the immune response. The project also aims to provide a better understanding of how MR and GR mediate the actions of immune-modulating glucocorticoid drugs such as prednisolone. Researchers will focus on the effects of MR activation on the inflammatory response and study how the MR and GR functionally interact to modulate gene transcription.
Objective
Glucocorticoids, such as cortisol, play an essential role in our stress response. Cortisol signals through two receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), and it has profound effects on the immune system. To date, much of the research on cortisol action has focused on the function of GR, but almost no work has been done on the function of MR. My main aim is to unravel the role of MR in mediating the effects of cortisol on the immune response, and I would like to answer two questions: 1) How does MR activation modulate the inflammatory response? 2) How do MR and GR functionally interact to alter gene transcription? I will use an interdisciplinary approach. The first question will be answered using the zebrafish animal model, and I will determine the role of MR in wounding-induced leukocyte migration in zebrafish larvae and study the mechanism of action of MR in activated macrophages. The second question will be answered using cultured macrophages, and I will determine the occurrence of MR/GR heterodimers using biophysical approaches, and establish a functional role of the heterodimers. The outcome of this project will have a considerable impact on the current paradigm of glucocorticoid action in the immune system, and extend our understanding of the molecular actions of immune-modulating glucocorticoid drugs. My training objectives are: 1) Broadening my expertise in endocrine research using the zebrafish model system. 2) Expanding my toolbox using cell culture-based approaches and biophysics. 3) Developing complementary skills required for the management and organization of an academic research group. Furthermore, I will strengthen my scientific track record and network. The project will be performed at the Institute of Biology of Leiden University, and implementation of the project in that environment will ensure a unique position for me to run this project successfully, receive appropriate training and advance my career.
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
- natural sciences biological sciences biophysics
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2019
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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.
2311 EZ Leiden
Netherlands
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.