WNT signalling in human trophectoderm development

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I seek to discover the processes that underlie early placenta development. We know that the correct functioning of the placenta is crucial for both mother and baby. After a human egg is fertilised, the cells multiply as the embryo grows. After five days the embryo is called a blastocyst and is made up of around 100 cells. Around 90% of these cells, called trophectoderm cells, will go on to form the trophoblast cells in the placenta. Early pregnancy is often described as a "black box," and due to the difficulties accessing the developing conceptus, we know very little about the key genes and signalling pathways that control the development of the trophectoderm and trophoblast. However, advances in human embryo research and the in vitro models we have to study trophoblast now open up the opportunity to investigate early placenta development. The aim of my research is to identify signalling pathways that are essential for placenta development. From my studies in the human blastocyst, I have identified a pathway called the "WNT signalling pathway" that I hypothesise controls the maturation of trophectoderm into trophoblast. I will test this hypothesis by using advanced imaging techniques to confirm that WNT signalling is active in the embryo. I will investigate the role of this pathway by blocking its activity using precise molecular tools and examining its effect on cell proliferation and gene expression. As human embryos are a limited resource, I will take advantage of in vitro models to refine the molecular tools and techniques I will use to study WNT signalling before applying them to embryos. This approach has the added advantage of deepening our understanding of the relationship between the models and the cell types they represent. These studies will yield novel insights into early human placenta development. In turn, if we understand how these processes work in healthy pregnancies we can begin to understand what defects may underlie complications of pregnancy. This knowledge could inform the understanding and treatment of infertility and placenta diseases such as preeclampsia, miscarriage, and stillbirth.