Objective
Homeostatic platelet counts are crucial for vascular integrity and vital to life. Megakaryocytes (MEKs) are giant hematopoietic cells forming large protrusions that fragment to constantly replenish the circulating platelet pool. Nevertheless, severe blood loss, sepsis and aggressive cancer therapies, often cause critically low platelet levels - a major public health problem in Europe's aging population. Despite the unmet clinical need to control platelet production, there is a major lack of knowledge about the mechanistic cell biology of MEKs, hampering the development of innovative therapies. MEKanics will go beyond the state of the art and proposes a combined cell biological and biophysical approach to study MEKs in physiological tissue environments to uncover the mechanical principles that drive platelet formation. I will use quantitative microscopy to characterize cytoskeletal dynamics of MEKs confined in 3D environments of controlled adhesiveness, geometry and stiffness to reveal the mechanisms of force generation and transmission critical for MEK protrusion formation. Further, I will explore how protrusion mechanics affect cytoplasmic transport and partitioning of organelles required for functional platelets. Using super-resolution intravital imaging, I will investigate these processes in their physiological bone marrow niche. By integrating scRNAseq and live-cell microscopy, I will map morpho-dynamics with transcriptomics to identify the gene signature initiating protrusion formation of MEKs in response to mechanical stimuli. A novel MEK cell-system with optimized access to genetic manipulations will allow high-throughput screening of candidate genes. Together, the unique combination of genetics, engineering, quantitative microscopy and intravital tools will provide a holistic cell mechanical model of MEKs in 3D tissues paving the way for new therapeutic approaches to control platelet formation and to advance devices for large-scale platelet production.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences physical sciences optics microscopy super resolution microscopy
- medical and health sciences clinical medicine oncology
- natural sciences mathematics pure mathematics geometry
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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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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
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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) ERC-2022-STG
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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.
80539 MUNCHEN
Germany
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.