Mechanism of damage to a fetus from signalling from the placenta

In two papers published in Nature Nanotechnology we have discovered a new and indirect mechanism for damage to a fetus in pregnancy. Here a variety of toxicants cause a bilayed trophoblast cell barrier, such as occurs between mother and fetus in the placenta, to send signals that damage cells on the other side of the barrier including human embryonic stem cells.


More recent work has shown that the process of signalling will damage neurones from the central nervous system and blood cells. A variety of signalling molecule are released from the barrier. The signalling occurs across bilayered trophoblast barriers, which are seen in vivo in the first trimester of pregnancy when the baby is most vulnerable to damage. It is not seen across predominantly monolayered barriers, which are a feature of the barrier at term in pregnancy when the baby is less vulnerable. The mechanism of signalling within the barrier involves ATP transmission across connexin and pannexin channels( gap junctions and hemichannels) and Ca wave propogation
We wish to explore this signalling process in the PhD studentship. A convenient exposure will use nanoparticles of various types
The applicant will assay the release of molecules and then examine their effects on different cell types including human embryonic stem cells and developing neurones. This is a multidisciplinary project and as such the application will learn a variety of new techniques
It an exciting a challenging investigation with direct implications to human biology and disease.