Understanding placental peptide hormones

The human placenta is the first organ of the embryo and it is functional immediately after implantation. Before fetal organogenesis, the placenta holds a multi-functional and unique role as a physical, chemical, and cellular barrier. It alone orchestrates the chemical communication between mother and fetus. Most of this communication is mediated by the secretion of specific placental peptide hormones (hCG, hPL, etc.) into the maternal bloodstream. Despite these hormones having developmental and irreplaceable functions, little is known about their intracellular life: synthesis, intracellular traffic, secretion, and degradation. More importantly, many pregnancy disorders are associated with lower expression and levels of these hormones in circulation, such as fetal growth restriction and preterm birth. The cell biology of these diseases is not well understood.

With the recent advance in human placenta organoid development and novel culture techniques of trophoblasts derived from stem cells, we can now finally interrogate the fundamental questions about placental hormones' intra and extra-cellular fate. In combination with the diverse set of advanced imagining methods available between the co-mentors of this project (advanced fluorescence and cryo-electron microscopy), innovative multi-omics techniques, and advanced biochemistry and cell biology approaches, we propose to 1) discover the diversity of secretory granules (SGs) expressed in and secreted from the human placenta; 2) implement a novel in vitro secretomics approach to determine the molecular machinery that regulates the secretion of the SGs and their content; 3) validate the mechanisms using human placenta and isolated trophoblasts from donated tissue and new placenta organoids culture.

The successful candidate will have the opportunity to train on several modern imaging techniques and learn about the fundamentals of placenta development and physiology while using a multi-disciplinary approach in a team of expert cell biologists from both institutions and generating impactful basic and applied research.