Our laboratory is a young and vibrant research group embedded in the Department of Development and Regeneration, focusing on calcium signalling during reproduction, and more specifically placental development. The placenta arbitrates developmental outcome; embryogenesis cannot progress without a functional placenta. Moreover, size at birth, and thus placental transport capacity, is critical in determining life expectancy as it affects mortality and morbidity in neonates and adults. Understanding placental pathologies, however, represents a clinical conundrum as the molecular requirements that underpin normal placentation are poorly understood. This research has the ambition to shed light onto placental development in mice and humans, with an unconventional view set on the regulatory role of calcium.
The research group has a strong and long-standing connection with the UZ Leuven hospital and has a strong network with other departments of the university and abroad, which warrants innovative and high-quality research. Our group is based on transparency, communication and integrity to promote a healthy research culture.
The nutrient-supplying function of the placenta is attributed to the formation of an extensively branched villous structure, failure of which is associated with poor fetal outcome. We have gained strong evidence that calcium is involved in signalling pathways that are imperative for normal placental development and thus fetal outcomes. This PhD project has the ambition to unravel how calcium ions can modulate trophoblast differentiation and thereby orchestrate branching morphogenesis.
The novelty of this work lies in the use of the recently established microCT imaging, conditional gene manipulations in mouse models, live cell imaging of calcium in trophoblast cells and the application of CRISPR/Cas9 – mediated gene targeting in mouse and human trophoblast stem cells. These techniques will be complemented by state-of-the art techniques including single-nucleus transcriptome analysis, functional assays on human trophoblast stem cells and trophoblast organoids.
This PhD research assumes a unique, and currently understudied, perspective in the investigation of placental development by focusing on the role of calcium in trophoblast differentiation, and holds great potential for an alternative approach of treating or screening pregnancy complications, such as recurrent miscarriage or fetal growth retardation.
For more information, please contact prof. dr. Katrien De Clercq, mail: katrien.declercq@kuleuven.be.
Interviews will take place in June. Intended project start date: no later than September 2024.
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