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An integrated experimental and mathematical approach to investigating endothelial barrier integrity in health and cerebral malaria

Project description

Understanding endothelial dysfunction in cerebral malaria

The endothelial barrier in the brain, primarily represented by the blood-brain barrier (BBB), is a highly selective and protective structure that regulates the exchange of substances between the blood and the brain. In cerebral malaria, a severe complication of the disease, the BBB is compromised, leading to brain inflammation and neurological damage. With the support of the Marie Skłodowska-Curie Actions programme, the CMEndoMod project aims to investigate the underlying molecular mechanisms that disrupt the BBB in malaria. Researchers will combine advanced in vitro experimental techniques to study endothelial function and dysfunction. The generated data will inform a multi-scale mathematical model, potentially guiding therapeutic strategies for cerebral malaria

Objective

The integrity of the endothelial barrier is vital for maintaining healthy brain function and is especially compromised in pathological conditions such as cerebral malaria. Despite its significance, the current understanding of the mechano-chemical mechanisms operating at sub-cellular, inter-cellular, and tissue scales within endothelial barriers during cerebral malaria remains limited. This project aims to close this knowledge gap by integrating advanced in vitro experimental methods with multi-scale mathematical models. Through a multi-tiered methodologyincluding single-cell assays, 2D endothelial monolayer cultures, and 3D brain microfluidic deviceswe plan to assemble a comprehensive dataset that captures the complex mechano-chemical processes underlying endothelial function and dysfunction. This rich dataset will facilitate the data-driven development, calibration, and validation of a new multi-scale mathematical model, along with a high-performance computational framework for its solution. The validated models will subsequently be used to design targeted experiments aimed at dissecting the molecular mechanisms regulating endothelial integrity. Our interdisciplinary approach is uniquely poised to cultivate a dynamic interplay between experimental data and mathematical modelling, leading to a more holistic understanding of the mechanisms responsible for endothelial integrity in healthy states and how they are compromised in the cerebral malaria condition. Ultimately, this strategy aims to provide an in-depth understanding of the endothelium, which could, in the long term, aid in the development of therapeutic interventions for cerebral malaria.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution

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.

€ 181 152,96
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost

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