Revolutionising cerebral malaria research with cutting-edge techniques

Maria Bernabeu

European Molecular Biology Laboratory (EMBL Barcelona), Spain

Cerebral malaria is a severe and often fatal form of malaria that affects the brain, causing significant damage to blood vessels. However, the brain remains a black box for the study of malaria and other neurovascular diseases. This project aims to tackle this issue by integrating research in pioneering 3D organs-on- chip, with advanced analysis tools on preserved brain tissue samples from deceased patients.

The goal is to create a detailed atlas map of cell types and their damage markers in malaria patients. In parallel, researchers will develop an advanced 3D model of brain blood vessels in the lab, including microglia, the main immune cell in the brain. The model will be exposed to malaria-infected blood cells to track how damage occurs. The findings from both real brain tissue and the lab model will be compared using powerful computational analysis to refine the 3D model, making it more accurate. Then, the improved model will be used to test drugs that could prevent or lessen blood vessel damage in cerebral malaria, aiming to reduce the mortality and long-term disability associated with this disease.

Taken together, the results from this project will include a detailed map of molecular signatures in cerebral malaria, and it will be the first 3D model incorporating microglia as the master regulator of immune responses in the brain. Together this will result in identification of key pathways leading to blood-brain barrier breakdown, which in turn should allow us to identify treatments to improve patient outcomes. This research is crucial for understanding and treating cerebral malaria and has also broader implications in developing technologies for research in other brain and vascular diseases, including stroke or Alzheimer’s.

• Christopher Moxon, School of infection and immunity, College of Medical, Veterninary and Life Sciences, University of Glasgow

Brain Integrative spatial data to generate new engineered 3D cerebral malaria models and treatments

€996.910,04