About the Project
Every cell carries a record of its past. Somatic mutations and DNA methylation changes accumulate as cells divide and as tissues encounter chemicals in the environment, leaving marks that reveal how tissues are built, maintained, and damaged [1,2,3]. Being able to read these records one cell at a time, whilst retaining each cell's position in the tissue, would show how clones expand, how exposures remodel tissues, and how these processes change with age and disease. However, the tools to do this…
at scale do not yet exist. This PhD project will help to build and apply these technologies in the newly established Tissue Biology Group at the MRC Laboratory of Medical Sciences.
The project sits within three connected areas of technology development in the group. The first is spatial lineage tracing, building on the Slide-tags platform [4] to recover lineage information, such as somatic mutations and DNA methylation barcodes, together with spatial coordinates in intact human tissue. The second is exposure screening, in which human-relevant in vitro systems such as organoids and primary cells are exposed to many chemicals and doses in parallel, with multiplexed sequencing readouts that report on mechanism. The third is the further development of spatial and single-cell sequencing methods themselves, to make them more sensitive, scalable, and widely usable. The exact focus will be agreed with you after you join, based on your interests and background, and on synergies with other work in the group. Once these technologies are established, you will use them to ask how exposures perturb human cells and tissues, by generating and analysing your own data.
You will be trained in both experimental and computational approaches, and will be supported to build on your strengths while developing skills in the other. Training is likely to include single-cell and spatial genomics library preparation, cell and tissue handling, analysis of sequencing data in R or Python, and building and benchmarking new methods, with support from the LMS core facilities in genomics, flow cytometry, light microscopy, and scientific computing. You will join a collaborative group that values mentorship at every level, work alongside postdoctoral scientists, and will likely collaborate with researchers within and outside the institute. You will be encouraged to present your work at international meetings and to publish it, with methods shared openly and scope for the technologies to be taken up beyond the group, including through commercialisation. No prior experience of these methods is required, only curiosity, creativity, and a strong interest in genomics and quantitative biology.
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
- Moore L, et al. The mutational landscape of human somatic and germline cells. Nature 597, 381-386 (2021). https://doi.org/10.1038/s41586-021-03822-7
- Gabbutt C, et al. Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues. Nat Biotechnol 40, 720-730 (2022). https://doi.org/10.1038/s41587-021-01109-w
- Kucab JE, et al. A compendium of mutational signatures of environmental agents. Cell 177, 821-836 (2019). https://doi.org/10.1016/j.cell.2019.03.001
- Russell AJC, et al. Slide-tags enables single-nucleus barcoding for multimodal spatial genomics. Nature 625, 101-109 (2024). https://doi.org/10.1038/s41586-023-06837-4