Fully-funded PhD: Development of a cell-based model to understand placental damage in pre-eclampsia and test novel therapeutic approaches

Pre-eclampsia is a common pregnancy disorder associated with increased risk of fetal complications such as fetal growth restriction, pre-term delivery and stillbirth. Early onset pre-eclampsia, caused by the failure of spiral arteries to adapt during pregnancy results in reduced blood flow to the placenta and a disturbed pattern of flow. Placental cells in contact with maternal blood called syncytiotrophoblasts are subsequently damaged by the altered haemodynamics. However, the molecular mechanisms are not fully understood and the impact on haemostasis remains unclear.

In this exciting PhD project, we aim to develop a simple and reproducible cell-based model to investigate how the changes in blood flow associated with pre-eclampsia damage the syncytiotrophoblasts, leading to the detrimental release of factors into the maternal blood. We will also investigate whether altered flow patterns contribute to fibrin deposition. This will further our understanding of the mechanisms responsible for early-onset pre-eclampsia and may help to inform new treatment strategies. The model will also provide a novel platform to test new drugs which preserve syncytiotrophoblast function and protect against pre-eclampsia.

Project aims and objectives

The aim of the study is to develop a simple, reproducible in vitro model to investigate the effects of altered haemodynamics associated with pre-eclampsia on haemostasis regulation in the placenta. The project will involve establishing a microfluidic system to perfuse syncytiotrophoblasts (differentiated from a trophoblast cell line) under different haemodynamic conditions to mimic maternal blood flow in the placenta in normal and pre-eclamptic pregnancies. The effects of altered haemodynamics on haemostasis regulation will then be determined using a combination of functional assays (thrombosis and haemostasis) and omics techniques.