Job Description

The Crick PhD program is open and there are amazing projects. I couldn’t recommend enough joining the program: brilliant community and excellent training and mentorship. Specific project in our lab will be decided based on your own interests.

Project background and description

The Santos lab studies fate specification and cell identity in the context of development and disease, using 2D and 3D stem cell-based models of human development as a model system. 

Cell division is a fundamental cellular process and the evolutionarily conserved networks that control cell division cycles adapt during development, tissue regeneration, cell de-differentiation and reprogramming, and a variety of pathological conditions, including cancer. 

Cell division is dependent on the activation and de-activation cycles of cyclin-dependent kinase complexes and the switching between DNA duplication and DNA segregation in all cells. The existence of these evolutionary conserved core regulators of both the embryonic and the somatic cell cycles, suggests that the fundamental principles that regulate both cycles are similar. 

However, the embryonic and the somatic cell cycles are very different. Divisions in the embryo are clocklike, fast, short and synchronous with no checkpoints or gap phases. With time, during lineage specification, these divisions become longer and asynchronous. The resulting somatic like cycles have checkpoint control and long gap phases, and the initiation of events is dependent on completion of early events, just like a falling domino. The question, thus, arises on how do the
same cell cycle regulators self-organize and adapt to drive different cell division cycles? 

To address this question, the potential student will use multi-disciplinary approaches including live cell imaging of embryonic stem cells expressing cell cycle and fate biosensors, genome editing techniques and single cell RNAseq approaches to gain mechanistic understanding into how the cell cycle remodels during embryonic stem cell differentiation and contributes to lineage specification in the developing embryo. 

Our recent work has shown that the way cells divide is part of their identity and we want to explore how changes in cell cycle bias cell fate in early development. 

These studies will have profound implications for understanding both normal development, reprograming and the transition to disease states, such as cancer, where cell identity and cell cycle regulation take a central stage.

Lab techniques include

The student will make use of 2D and 3D human embryonic stem cell-based models of human development, live cell imaging and advanced microscopy, CRISPR, biosensors, single cell approaches, genomics, proteomics, image analysis and bioinformatics

Key words: embryonic stem cells, cell cycle, cell decision-making, developmental biology, cancer 

Note: This is just one example of the sort of project that is available in the Santos lab. The precise project will be decided on in consultation with the supervisor

More information about the lab, please visit https://www.crick.ac.uk/research/labs/silvia-santos
and check out our Bluesky: @Santoslab and Twitter: @SantosLaB8 

Candidate background

This project will suit any candidate who is intrigued by stem cells, cell division and/or fate decisions and cell identity and who is keen to learn more about Developmental and Cell Biology. 

Any degree in the Life Sciences is suitable for applying for this studentship. A strong commitment to doing research and motivation to be exposed to different state of the art techniques including single cell technologies and imaging is essential. 

Motivation to be in an interdisciplinary, collegial and highly collaborative environment and learn quantitative approaches is an asset.

References

1. Gharibi, B., Inge, O.C.K., Rodriguez-Hernandez, I., Driscoll, P.C., Dubois, C., Jiang, M., . . . Santos, S.D.M. (2025) Post-gastrulation amnioids as a stem cell-derived model of human extra-embryonic development. Cell 188: 3757-3774 .e3720. PubMed abstract
2. Gunne-Braden, A., Sullivan, A., Gharibi, B., Sheriff, R.S.M., Maity, A., Wang, Y.F., . . . Santos, S.D.M. (2020) GATA3 mediates a fast, irreversible commitment to BMP4-driven differentiation in human embryonic stem cells. Cell Stem Cell 26: 693-706.e699. PubMed abstract
3. Padgett, J. and Santos, S.D.M. (2020) From clocks to dominoes: lessons on cell cycle remodelling from embryonic stem cells. FEBS Letters 594: 2031-2045. PubMed abstract
4. Araujo, A.R., Gelens, L., Sheriff, R.S.M. and Santos, S.D.M. (2016) Positive feedback keeps duration of mitosis temporally insulated from upstream cell-cycle events. Molecular Cell 64: 362-375. PubMed abstract
5. White, J. and Dalton, S. (2005) Cell cycle control of embryonic stem cells. Stem Cell Reviews 1: 131-138. PubMed abstract