A 2026 Crick PhD project with Frank Uhlmann.

Project background and description

In the Chromosome Segregation Laboratory, we investigate molecular mechanisms that underpin faithful chromosome segregation during cell division. We use various model organisms to study the contribution of Structural Maintenance of Chromosome (SMC) complexes to sister chromatid cohesion and chromosome condensation, essential processes that ensure faithful segregation of centimetre-long chromosomal DNA molecules within micrometre-sized cells. In this project, we will investigate how the SMC complex ‘Cohesin’ fulfils a second important role by building interphase chromatin architectural features, including chromatin loops and topologically associating domains. Widely recognised as contributing to genome organisation and transcriptional control, the mechanism by which cohesin shapes the interphase genome remains incompletely understood. This project will use chemical biology and genomics tool development to visualise the real-time behaviour of Cohesin while it builds interphase chromatin architectural features. The outcome will inform our understanding not only of Cohesin function, but also of how the wider family of SMC complexes act in genome organisation and stability.

Below is a recent review on the subject [1], as well as research publications from the last four PhD students who graduated from our laboratory [2-5].

Candidate background

This project requires a strong interest in molecular mechanisms that underpin fundamental cellular processes, in this case interphase chromatin organisation in the cell nucleus. A background in, and experience with, genomics techniques and computational data analysis will be an advantage.

References

1. Uhlmann, F. (2025)

            A unified model for cohesin function in sisterchromatid cohesion and chromatin loop formation.