Project description
A river runs through it: blood and lymphatic vessel formation in the extracellular matrix
Blood and lymph travel through the body in blood and lymphatic vessels, respectively, which form intricate networks throughout the tissues. Blood transports gases, nutrients and metabolic waste. The lymphatic system drains excess fluids and proteins from the body’s tissues and returns them to the bloodstream, preventing swelling. Researchers recently showed that the stiffness of the extracellular matrix (ECM) affects the formation of new lymph vessels. With the support of the Marie Skłodowska-Curie Actions programme, the STRomA project is investigating the role of ECM stiffness in the formation of new capillaries and lymphatic vessels, with the goal of highlighting mechanistic similarities and differences.
Objective
Endothelial cells (ECs) recognize and respond to mechanical forces through their cell-cell and cell-matrix adhesions and translate physical stimuli into biological responses in a process called mechanotransduction. The composition and mechanical properties of the extracellular matrix (ECM) differ across the vascular tree, in its surrounding tissues and in development and diseases, such as edema formation. I have recently shown for the first time that ECM stiffness fundamentally controls lymphangiogenesis. I hypothesize that changes in ECM stiffness are a key regulatory mechanism of angiogenic processes in development and disease. A comprehensive analysis of novel ECM stiffness-regulated genes is pivotal to understand these processes integrally. In a preliminary study, I have performed differential RNA sequencing of blood (B) and lymphatic (L) ECs cultured on soft and stiff matrices. 3200 genes were regulated similarly in BECs and LECs in response to changes in matrix stiffness. Interestingly, the same number of genes was differently regulated. In the next two years, I will study the role of selected genes in lymphangiogenesis and angiogenesis in vitro and in transgenic mouse models with state-of-the-art microscope and live imaging techniques. First, I will analyze an actin-regulating protein family that is significantly regulated by matrix stiffness in both, BEC and LECs, suggesting a more general role in lymphangiogenesis and angiogenesis by regulating cytoskeletal dynamics. Second, I will study a molecule, which is involved in intracellular cGMP signaling and is predominantly regulated in LECs, suggesting a more specific role in lymphangiogenesis. Last, I will generate an in vitro fluorescent stiffness sensor to live-visualize changes in stiffness inside the EC. Ultimately, the proposed action can provide novel targets to modulate lymph and blood vessel formation with implications for edema treatment and will support me to become an independent group leader.
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 genetics
- medical and health sciences clinical medicine angiology
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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-EF-ST - Standard EF
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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-2018
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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.
20251 Hamburg
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.