structure determination, and DNA sequencing approaches.
Our laboratory has pioneered several of the key advances driving this field forward, combining biochemical reconstitution, functional DNA replication assays, and structural biology to investigate replisome structure, function, and mechanism. We achieved the first reconstitution of functional human replisomes from purified proteins and have since determined several human replisome structures by cryo-EM. Building on this platform, we will spend the coming years watching the human replication machinery in action — capturing, at near-atomic resolution, how it is assembled, how it navigates the genome during normal DNA replication and how it responds when it collides with obstacles such as DNA damage and protein barriers.
We are seeking an ambitious and enthusiastic PhD student to join our research group and undertake a project addressing a key, currently unresolved question in human replisome function. You will gain extensive experience in protein purification, complex biochemical reconstitution, and structural biology, particularly cryo-EM. We are a medium-sized, open, and collaborative lab: everyone works closely together, ideas and troubleshooting are shared freely across the group, and you'll be supported to learn new techniques directly at the bench rather than working in isolation. This hands-on culture provides an excellent environment in which to develop as an independent researcher while always having supportive and knowledgable colleagues close at hand.
Funding Notes
Competition Funded PhD Project (Students Worldwide)
References
- Roske, J.J., Yeeles, J.T.P., (2024) Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand polymerase Pol ε. Nature Structural and Molecular Biology. 10.1038/s41594-024-01370-y.
- Jones, M.L., Aria, V., Baris, Y., Yeeles, J.T.P., (2023) How Pol α-primase is targeted to replisome to prime eukaryotic DNA replication. Molecular Cell. 10.1016/j.molcel.2023.06.035.
- Baris, Y., Taylor M.R.G., Aria, V. and Yeeles, J.T.P. (2022). Fast and efficient DNA replication with purified human proteins. Nature. 10.1038/s41586-022-04759-1.
- Jenkyn-Bedford, M., Jones, M.L., Baris, Y., Labib, K.P.M., Cannone, G., Yeeles, J.T.P., and Deegan, T.D. (2021). A Conserved Mechanism for Regulating Replisome Disassembly in Eukaryotes. Nature. 10.1038/s41586-021-04145-3.
