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

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.