LSI and BBSRC funded PhD studentships are available to study early human embryo development using stem cell models
How a complex structure, an embryo, forms from a single cell is a fascinating fundamental biology question. Understanding early human embryo development will also have applications in reproductive medicine. However, research is limited by availability of human embryos and ethical considerations. Therefore, our concept of human early embryo development draws heavily on mouse studies. However human embryos differ in many respects including timescale and formation of a bilaminar embryonic disc as the substrate for gastrulation. We recently established a stem cell based human blastocyst model (the “blastoid”), that recapitulates the morphology and cellular composition of natural human blastocysts. This blastocyst model provides a unique experimental platform to investigate human developmental dynamics using genetic, molecular and bioengineering approaches. In this project the PhD student will implement a microfluidic system to mimic the in utero biophysical environment and empower further development of the blastoid. You will then undertake high resolution 3D time-lapse imaging using a cutting edge advanced light sheet microscope. You will map the developmental dynamics at cellular resolution by live cell tracking using fluorescent lineage reporters that you will create using CRISPR/Cas 9 technology. Building on this technical platform you will explore the molecular regulatory mechanism of human hypoblast differentiation and bilaminar disc formation, involving single cell transcriptomic analyses. The project integrates embryology, stem cell biology, molecular biology, transcriptomics, biophysics and bioimaging.
Yanagida A. et al, Naive stem cell blastocyst model captures human embryo lineage segregation. Cell Stem Cell 28, 1016-102.
Guo G. etal, Human naive epiblast cells possess unrestricted lineage potential. Cell Stem Cell 28, 1040-1056 e1046.
LSI PhD programme: https://www.exeter.ac.uk/study/funding/award/?id=4533Application