About the Project
Zygotic genome activation (ZGA) marks the transition from maternal to embryonic control of development and provides a tractable system in which to examine how regulatory genome function is established (1). Recent work from the Vaquerizas laboratory has shown that chromatin architecture is extensively reorganized before and during ZGA, including the emergence of loops and insulation prior to major transcriptional activation in Drosophila (2). Related studies from the laboratory further indicate…
that major developmental transitions are accompanied by substantial rewiring of higher-order genome organization and regulatory state (3). These observations argue that ZGA should be analysed not simply as a transcriptional event, but as a coordinated process linking chromatin folding, cis-regulatory activity and cellular context. This project will address that problem by investigating how spatial and three-dimensional genome organization are coupled during genome activation in the early embryo.
The project will combine low-input chromosome conformation approaches established in the Vaquerizas laboratory, including Pico-C, with spatially resolved genomics methods available through the Russell laboratory, in particular Slide-tags, and potentially Xenium-based imaging approaches where appropriate. The central aim will be to define how promoter-enhancer communication, boundary formation, insulation and related architectural features are deployed during ZGA, and how these features map onto spatially restricted transcriptional states in intact embryonic material. Depending on the system and question selected, the work may also incorporate long-read sequencing to resolve isoform usage, haplotype-resolved transcription or allele-specific regulation in spatially defined embryonic contexts. The balance between experimental and computational work will be shaped by the specific direction of the project, but will involve integrative analysis of multimodal datasets at single-cell or single-nucleus resolution.
The precise biological question is intentionally kept broad within this framework so that the student can develop a focused project at the interface of developmental genomics, chromatin biology and spatial omics. This flexibility is supported by recent work from both groups, including the application of Xenium-based spatial transcriptomics in mouse embryos (4), the development of Slide-tags for multimodal spatial genomics (5), and recent spatial and regulatory atlases from the laboratory (6). The student will therefore be well positioned to define and test mechanistic hypotheses on how an active regulatory genome is established in space and time at the onset of embryonic transcription.
To apply for this project please follow the application instructions provided on the LMS website (https://lms.mrc.ac.uk/work-and-study/studentships/lms-4-year-phd-studentships/) and submit an application form by the deadline. 'Registering your interest' below will not be considered an application.
Funding Notes
This studentship covers all tuition fees as well as a tax free stipend amounting to £26,500pa paid directly to the student in monthly instalments.
The funding is available for both Home and Overseas students.
References
- Ing-Simmons E, Rigau M, Vaquerizas JM. Emerging mechanisms and dynamics of three-dimensional genome organisation at zygotic genome activation. Curr Opin Cell Biol. 2022;74:37–46.
- Maziak N, Zhang Y, Groll F, Brown HE, Madich A, Kaur Y, Harrison MM, Zhou J, Vaquerizas JM. Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila. Nat Genet. 2026;58:607–617.
- Huang X, Chen X, Feng S, Liu Z, Sun Y, Yao X, Li F, Zhu W, Gao L, et al. Global reorganization of genome architecture at the transition to gametogenesis. Nat Struct Mol Biol. 2026.
- Amblard I, Kalaitzis CM, Balaguer Balsells I, Andrew I, Choi KL, Moka HA, Game L, Vaquerizas JM, Metzis V. Temporally distinct CDX programmes preconfigure vagal and trunk neural crest. bioRxiv. 2026. doi:10.64898/2026.07.13.738216.
- Russell AJC, Weir JA, Nadaf NM, Shabet M, Kumar V, Kambhampati S, Raichur R, Marrero GJ, Liu S, et al. Slide-tags enables single-nucleus barcoding for multimodal spatial genomics. Nature. 2024;625:101–109.
- Bhaskaran J, Ing-Simmons E, Balaguer Balsells I, Di Persio S, Chan MMY, Politz M, Cremers JF, Rotte N, Kliesch S, et al. A single-nucleus multiomic and spatial atlas of gene regulation in human spermatogenesis. bioRxiv. 2026. doi:10.64898/2026.09.04.749409.