Tag - DNA replication

VACANCY: Enterprise DTP iCASE Doctoral Training Programme studentship

Project title: Developing advanced mass photometry methods for analysis of the multi-step helicase loading process
Lead supervisor: Christian Speck
Funding: EPSRC
Start date: October 2021
Duration: 3.5 years
Date posted: 12 November 2020
Closing date: 07 January 2021

The student will use and develop a novel single-molecule biophysical method (mass photometry) to investigate a key step in DNA replication, the loading of the replicative helicase on DNA, and explore this multi-step reaction in a time resolved manner. This work will address how DNA replication works and contribute to the development of helicase loading inhibitors as a potential anti-cancer therapy.

The project is a collaboration between Refeyn Ltd and the Imperial College London research groups of Christian Speck and David Rueda.  Refeyn, a company based in Oxford, has recently developed and brought to market a breakthrough technology that measures the molecular weight of individual proteins and protein complexes by mass photometry.  This revolutionary biophysical technique is highly-accurate, very fast, label-free and allows the use of native proteins.

The group of Christian Speck, which includes seven postdocs, three PhD students and two technicians, applies a range of biochemical, structural, proteomic and genetic/genomic approaches in order to investigate DNA replication and chromatin structure.  The Group works in a highly collaborative way and provides PhD students with a multidisciplinary learning environment.  Applicants that interested in genome stability and method development and have a good background in biochemistry or biophysics are strongly encouraged to apply.

Interested candidates can contact Christian Speck directly for more information.

Enterprise DTP: iCASE Doctoral Training Programme | Project details | Apply

New paper on the structural mechanism of helicase loading

Yuan, Z., Schneider, S., Dodd, T., Riera, A., Bai, L., Yan, C., Magdalou, I., Ivanov, I., Stillman, B., Li, H., Speck, C. (2020). Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6. Proceedings of the National Academy of Sciences of the United States of America 117, 17747-17756.
Abstract | Full Text |

New paper proposes lagging-strand DNA extrusion mechanism

Noguchi, Y., Yuan, Z., Bai, L., Schneider, S., Zhao, G., Stillman, B., Speck, C., Li, H. (2017). Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. Proceedings of the National Academy of Sciences of the United States of America 114, E9529-E9538.
Abstract | Full text |

New paper shows Cdc6 ATPase activity promotes DNA replication

Chang, F., Riera, A., Evrin, C., Sun, J., Li, H., Speck, C., Weinreich, M. (2015). Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication. eLife 4, e05759.
Abstract | Full text | Biomedical Picture of the Day | MRC Clinical Sciences Centre News | Imperial College London News |

New paper on regulation of loading of MCM2-7 onto DNA

Samel, S. A., Fernández-Cid, A., Sun, J., Riera, A., Tognetti, S., Herrera, C., Li, H., Speck, C. (2014). A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2–7 onto DNA. Genes & Development 28, 1653-1666.
Abstract | Imperial College London News |

Report on Keystone Symposium on ‘DNA Replication and Recombination’

A report of the Keystone Symposium ‘DNA Replication and Recombination’ held in Keystone, USA, 27 February to 4 March 2011.

Johansson, E., Speck, C. and Chabes, A. (2011). A top-down view on DNA replication and recombination from 9,000 feet above sea level. Genome Biology 12, 304.
| Full text |