About the Project
A 2027 Crick PhD project with Naomi Moris.
Project background and description
Gametes (sperm and egg) originate from progenitors called 'germ cells' that arise early in embryo development, and are crucial for the fertility of the offspring. Although they are specified around the time of gastrulation, germ cells must migrate through various tissues – including the endodermal tract – and mature towards specific fates, with unique transcriptional and epigenetic profiles. It is not well understood how this maturation process occurs, or how interactions between somatic cells…
and germ cell neighbours enables mature states to arise. We will use mouse and human gastruloids [1, 2] to explore how germ cells develop in vitro using gastruloids [3], with a focus on co-developmental interactions between germ cells and other somatic tissues. The candidate will examine the role of the endoderm and somatic tissues and the various signals that play a role in germ cell fate progression, using a range of characterisation techniques and perturbation experiments. The work will explore the role of signalling interactions in germ cell biology, with the potential to reveal insights into both fundamental developmental biology principles, with future implications for exploring mechanistic causes of infertility.
Candidate background
The project would suit candidates with a very strong background in developmental biology. Desirable skills include experience of stem cell culture, organoid/embryoid experience, and background in germline research.
Lab-specific question
What do you think is one of the most important unanswered questions in developmental biology, and what makes you think it is an important question to investigate?
Funding Notes
Successful applicants will be awarded a non-taxable annual stipend of £27,715 plus payment of university tuition fees. Students of all nationalities are eligible to apply.
References
- van den Brink, S.C., Baillie-Johnson, P., Balayo, T., Hadjantonakis, A.K., Nowotschin, S., Turner, D.A. and Martinez Arias, A. (2014) Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells. Development 141: 4231–4242.
- 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.
- Cooke, C.B., Barrington, C., Baillie-Benson, P., Nichols, J. and Moris, N. (2023) Gastruloid-derived primordial germ cell-like cells develop dynamically within integrated tissues. Development 150.
- Cooke, C.B. and Moris, N. (2021) Tissue and cell interactions in mammalian PGC development. Development 148.
