Imaging the dynamics of human implantation

Imaging the dynamics of human implantation schematic

Primary Supervisor: Kathy Niakan (kkn21@cam.ac.uk)

Second Supervisor: Naomi McGovern (nm390@cam.ac.uk)

Additional supervision: Thomas Rawlings, Geraldine Jowett and Tereza Cindrova-Davies

Host Department or Institute: Department of Physiology, Development and Neuroscience

Project description

Lineage tracing in human embryos is limited by the lack of indelible markers that permit long-term visualisation of all cells, precluding application to later stages of development. We have recently developed methods to image human embryo development up to 6 days to determine the timing of the first and second cell fate decision. 

Our future goal, and the aim of the PhD project, is to extend these studies to investigate timing of the subsequent cell fate specification events, up to 14 days post fertilisation, with a specific focus on implantation. The key objective is to visualise and quantitatively analyse the dynamics of placental cell migration, differentiation and endometrial remodelling. At implantation, placental progenitor cells are thought to attach and migrate into endometrial epithelial cells. The PhD student will label and visualise embryonic versus endometrial cells at implantation to understand how these tissues are remodelled. A significant challenge will be to segment and track cells in complex, growing multicellular structures. The student will collaborate with experts in advanced image analysis to extend segmentation, cell lineage and migration analysis by further developing deep learning and convolutional neural network analysis, establishing a generalisable toolkit for developmental biology and stem cell models.

We are working with Thomas Rawling and Tereza Cindrova-Davies who have contributed to pioneering endometrial modelling and extended culture studies. We have further improved on these models by establishing a highly robust multicellular culture that sustains embryonic development. In collaboration with Naomi McGovern and Geraldine Jowett (Loke CTR) we will re-establish the cellular complexity of endometrial tissue at implantation. In collaboration with Serena Best and Ruth Cameron (Material Sciences), we will further improve on the endometrial model for live imaging by applying principles of material sciences to generate physiologically-informed scaffolds. The ultimate goal is to decipher placental migration and coordinated remodelling of the embryo-endometrium interface.

Candidate background

Highly motivated and genuinely interested. Excellent communication skills are needed to gain training and expertise across multiple research groups. Interest in interdisciplinary research.

References

  1. Abdelbaki A., McCarthy A., Karsa A., Muresan L., Elder K., Papathanasiou A., Snell P., Christie L., Wilding M., Steventon B.J. and Niakan K.K. (2025) Live imaging human embryos reveals mitotic errors and lineage restriction prior to implantation. Nature Biotechnology. doi: 10.1038/s41587-025-02851-1
  2. Interactions between placental Hofbauer cells and L. monocytogenes change throughout gestation.Yoshida N, Appios A, Li Q, Hutton JP, Wood G, Potts M, Aleksandrowicz J, Barrozo ER, Dover F, Anderson H, Stephens K, Aye ILMH, Thomas JR, Schenk HCM, Bourke AM, Aiken CE, Moffett A, Sharkey A, V Protasio A, Aagaard KM, Edgar JR, Chung BYW, McGovern N. Sci Immunol. (2025) PMID: 40680145.
  3. Rawlings T.M., Makwana K., Taylor D.M., Molè M.A., Fishwick K.J., Tryfonos M., Odendaal J., Hawkes A., Zernicka-Goetz M., Hartshorne G.M., Brosens J.J. and Lucas E.S. (2021) Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids. eLife 10:e69603. https://doi.org/10.7554/eLife.69603
  4. Cindrova-Davies T., Zhao X., Elder K., Jones C.J.P., Moffett A., Burton G.J. and Turco M.Y. (2021) Menstrual flow as a non-invasive source of endometrial organoids. Communications Biology 4:651. https://doi.org/10.1038/s42003-021-02194-y
  5. Jowett G.M., Norman M.D.A., Yu T.T.L., Rosell Arévalo P., Hoogland D., Lust S.T., Read E., Hamrud E., Walters N.J., Niazi U., Chung M.W.H., Marciano D., Omer O.S., Zabinski T., Danovi D., Lord G.M., Hilborn J., Evans N.D., Dreiss C.A., Bozec L., Oommen O.P., Lorenz C.D., da Silva R.M.P., Neves J.F. and Gentleman E. (2021) ILC1 drive intestinal epithelial and matrix remodelling. Nature Materials 20:250–259. https://doi.org/10.1038/s41563-020-0783-8