Objective
Our bodies turn over billions of cells every day to keep us healthy. Old, damaged or excess cells need to be cleared, and professional and non-professional phagocytes engulf cells dying by apoptosis. The efficiency of this process is critical for homeostasis, minimising inflammation, and promoting organ function. Deficiencies in engulfment predispose to autoimmune and inflammatory diseases, and the host lab has shown that mice deficient in molecular components of engulfment exhibit exaggerated inflammatory responses.
We hypothesise that apoptotic cell phagocytosis can be boosted via small molecules that target the engulfment machinery, and that this could open new avenues for therapy in specific disease contexts. Here, I propose to perform an unbiased drug screen to identify small molecule candidates that can enhance apoptotic cell uptake – that is, a ‘gain of function’ screen for engulfment. The host lab has recently developed a fluorescence-based engulfment assay to quantitatively measure apoptotic cell uptake. I will develop this assay into a high-throughput screen to test a large library of compounds. I will address the consequences of pharmacologically enhanced engulfment on professional and non-professional phagocytes, and employ state-of-the-art nucleomics and proteomics approaches to explore the cellular targets of these candidate molecules. Finally, I will test whether the administration of small molecule ‘engulfment enhancers’ can be of benefit in inflammatory disease models relevant to human pathology. This proposal uniquely exploits the complementary expertise of the host lab (pathways of apoptotic cell clearance) and myself (inflammation and disease models), while benefitting from the significant resources of the host institute. While the mechanistic complexities of apoptotic cell clearance are just beginning to be deciphered, we anticipate that this study will also provide insight into molecular pathways of apoptotic cell uptake and processing.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences basic medicine pathology
- 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.1.3. - 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-2017
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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.
9052 ZWIJNAARDE - GENT
Belgium
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.