Modelling human development using embryonic stem cell-derived human gastruloids

A Crick PhD position for the 2021 programme in the lab of Naomi Moris.

Project background and description

Studying the development of the human embryo poses technical and ethical challenges that have limited our understanding of human development. This is especially true for the gastrulation stage, where the organisation of the body plan is established and when it is thought that certain birth defects, or congenital abnormalities, arise. Embryonic stem cells (ESCs) can be used to model various aspects of mammalian development, including the coordination of cell fate using new 3D ‘organoid’-like systems, called gastruloids [1, 2].

This project will make use of a new human gastruloid system [3] to investigate: (a) the emergence of different cell types and their spatiotemporal coordination in three-dimensional human gastruloids; (b) the relevance of this in vitro system to the development of the mammalian embryo in vivo; and (c) the possibilities for using human gastruloids as disease models of various congenital abnormalities with medical relevance. The precise details of the project will be decided on in consultation with the supervisor and the rest of the team.

The role will involve culturing human ESCs to generate gastruloids and using techniques such as confocal microscopy, single cell RNA-sequencing, live-imaging and genetic engineering. Training in molecular biology, cell biology, microscopy and bioinformatics will be provided.

Candidate background

This project would suit candidates from a biological / biochemical background with a keen interest in developmental biology and in the fundamental principles of embryo development.

Experience of human Embryonic Stem Cell (ESC) / iPSC culture would be advantageous, but is not a prerequisite.

References

 

1.       Beccari, L., Moris, N., Girgin, M., Turner, D.A., Baillie-Johnson, P., Cossy, A.-C., . . . Martinez Arias, A. (2018)

          Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids.

          Nature 562: 272-276. PubMed abstract

2.       van den Brink, S.C., Alemany, A., van Batenburg, V., Moris, N., Blotenburg, M., Vivie, J., . . . van Oudenaarden, A. (2020)

          Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids.

          Nature 582: 405-409. PubMed abstract

3.       Moris, N., Anlas, K., van den Brink, S.C., Alemany, A., Schröder, J., Ghimire, S., . . . Martinez Arias, A. (2020)

          An in vitro model of early anteroposterior organization during human development.

          Nature 582: 410-415. PubMed abstract