13 / 11 / 2023
Cell model to help understand Dengue fever
2023 Summer Studentship winner Konstantina Skandali is a final year Biomedical Sciences Student at the University of Surrey. Konstantina’s research is being supervised by Dr Paola Campagnolo, and she has been awarded £4,500. Her project develops a 3D model using multiple cell types to study how cells interact within capillaries when they become leaky and breakdown in haemorrhagic diseases.
Over half of the world’s population is at risk of dengue infection and five percent of patients infected go on to develop severe dengue, a potentially deadly syndrome characterised by leaky blood vessels causing haemorrhage and oedema and leading to multiple organ failure.
Pericytes are multi-functional cells of the circulatory system that wrap around endothelial cells lining capillaries throughout the body. Vascular dysfunction involving the detachment of pericytes from the capillaries is the basis of a wide range of life-threatening conditions including viral diseases such as severe dengue, but also diseases such as diabetes and cancers. Severe dengue haemorrhagic disease is currently studied in animals including mice, rabbits and non-human primates, which can cause them severe suffering.
Dengue virus produces a protein that circulates in patients’ blood and plays a role in blood vessel leakage, by disrupting the connections between the pericytes and endothelial cells.
Konstantina will replicate the interaction between endothelial cells and pericytes by growing them together in 3D aggregates called spheroids. She will study the organisation of the cells over time and record the changes after treating the cells with the dengue virus protein. She will also analyse molecules that might be involved in the dengue disruption of capillary cell interactions. Her data will be used to build a mathematical model of the cell dynamics within the spheroids to define the characteristics of dengue-induced vascular dysfunction.
A human cell-based 3D in vitro system that mimics and reproduces the development of vascular dysfunction will generate data that can then be used to model the system in silico. A combination of cell based and computational modelling will help reduce the use of animals in research and provide a robust and reproducible system to study vascular dysfunction mechanisms in a broad range of diseases that affect millions around the world.