About the Project
Second Supervisor: Professor Peijun Zhang, Nuffield Department of Medicine University of Oxford
The human genome is metres long but packed into cells only a few micrometres in diameter. To function correctly, DNA must be carefully organised so that essential processes such as gene expression, repair, replication, and cell division can occur. A key organiser is the cohesin complex, a ring-shaped protein machine that controls the structure of the genome. Cohesin can connect DNA regions within the same chromosome ("in cis") by reeling the DNA into loops, or hold sister chromatids together after DNA replication ("in trans") until they are separated during cell division. Both functions are vital for accurate gene regulation and genome stability.
Cohesin is regulated by partner proteins that determine where it binds, stabilises, or releases DNA. We have shown that several cohesin regulators use a common molecular motif to control cohesin, influencing whether it forms loops or maintains chromosome cohesion. This suggests that many such "ligands" form a broader system that directs cohesin activity at different stages of the cell cycle and across the genome.
This project will investigate how these ligands regulate cohesin's diverse roles. We will use cutting-edge methods, including single-particle cryo-EM and in cell cryo-ET to visualise protein structures and use biochemical assays and cell-based approaches to test biological outcomes. Together, these studies will reveal how cohesin control links three-dimensional genome organisation to key processes such as gene expression, DNA repair, and chromosome segregation. Understanding these mechanisms will provide fundamental insights into genome biology and how defects in cohesin regulation contribute to human disease.
Techniques that will be undertaken during the project
The project will use innovative methods including cryoEM and cryoET to integrate structural biology in vitro with biological imaging in situ. The aim is to adopt new technologies, andante to interdisciplinarity and cross-institutional collaboration.
Enquiries
Project Enquiries to daniel.panne@le.ac.uk
Programme enquiries to mibtp-admin@leicester.ac.uk
To apply please refer to
https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
Funding Notes
All MIBTP students will be provided with a 4 year studentship. This includes: Tuition fees at the UK fee rate*, a tax free stipend which for 2026/7 is £21,805 per year (2027/8 stipend to be confirmed), a travel allowance over years 1-3, a travel/conference budget, a generous consumables budget, use of a laptop for the duration of the programme. The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.