Project description
Unravelling cytokine-specific transcription factors in macrophages
Macrophages are an essential component of the immune system, involved in innate immunity and inflammation. They recognise, engulf, and destroy pathogens, debris, and dead cells through a process called phagocytosis. Many inflammatory diseases are associated with deregulated macrophage function. Funded by the European Research Council, the CYTOMAC project aims to delineate the specific action of cytokines on macrophage behaviour, given that despite their contrasting functions, they share similar signalling pathways. Researchers will focus on specific transcription factors responsible for cytokine-mediated activity. This research has the potential to enhance the development of targeted interventions for inflammatory diseases and improve available treatment options.
Objective
Dysregulated macrophage function underlies many inflammatory diseases. Cytokines, small secreted signaling molecules with immune-modulatory functions, shape the macrophages phenotype, thereby affecting disease states. Puzzlingly, many cytokines with opposing functions, utilize highly similar JAK-STAT signaling cascades, leaving it unclear how cytokine-specific responses can occur.
In my previous work, I studied enhancer activation in mouse macrophages from genetically different strains. By studying genetic variation, I found that transcription factor (TF) motifs crucial for enhancer activation can be identified. I further developed the bio-informatic tool MAGGIE to study TF motif mutations in different strains of mice, which subsequently enabled me to discover a novel TF important for enhancer activation by the cytokine interleukin-4.
Based on my findings, I hypothesize that cytokines require specific, yet unidentified TFs that cooperate with JAK-STAT signaling to mount cytokine-specific effects.
CYTOMAC aims to identify these cytokine-specific TFs downstream of JAK-STAT that direct appropriate cell responses. I will exploit the genetic variation across mouse strains and study enhancer activation in macrophages from these strains in response to different disease-related cytokines. Specifically, I will: (1) use genetic diversity between mouse strains to identify specific TFs regulating cytokine-specific responses; to then target these novel TFs in (2) mouse and (3) human macrophages and (4) translate my findings to human disease and inflammatory disease models.
Inhibitors targeting JAK-STAT show high potential in clinically treating inflammatory diseases, including rheumatoid arthritis. However, as they affect generic pathways of many cytokines they come with considerable side-effects, limiting applicability. CYTOMAC will reveal novel, cytokine-specific TFs, which will aid in developing better tailored intervention strategies.
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.
This project's classification has been validated by the project's team.
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.
This project's classification has been validated by the project's team.
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.
-
HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-ERC - HORIZON ERC Grants
See all projects funded under this funding scheme
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) ERC-2022-STG
See all projects funded under this callHost institution
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.
1081 HV Amsterdam
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.