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  Regulation of replication timing in mammalian cells


   School of Biological Sciences

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  Dr S Buonomo  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Interested individuals must follow Steps 1, 2 and 3 at this link on how to apply
http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

DNA replication is a key event for the transmission of genetic information. The eukaryotic genome does not replicate all at once, but it follows a temporal program that reproducibly ensures replication of different parts of the genome at different stages of S-phase. This is called the DNA replication-timing program. There are many circumstantial evidences connecting re-organization of nuclear architecture after mitosis and the establishment of the order of activation of origins of DNA replication. However, there is no proof that the latter depends on the former. In this project we will employ advanced genetic manipulation of mouse embryonic stem cells, protein engineering and genome-wide sequencing to resolve the long standing question of the molecular machinery linking nuclear architecture and the timing of DNA replication. We will also explore the effects of replication-timing perturbation on cellular aging and on the heterogeneous distribution of mutation rates and types between the early and late replicating genome.

The student will be involved at every stage of the project from generation of embryonic stem cells from transgenic mice and their genetic manipulation, to FACS sorting and bioinformatic analysis. This project offers therefore a great opportunity for learning a wide variety of state-of-the-art techniques while working in an exciting and fundamental area of biology.

If you are interested in cell cycle, DNA replication, nuclear organization and want to work with mammalian primary and stem cells join our group. We are looking for enthusiastic, flexible and hard working candidates driven by curiosity and passion for science. Basic knowledge of cell/molecular biology and ability to work in English, in an international environment are required.

Funding Notes

Please follow the instructions on how to apply http://www.ed.ac.uk/biology/prospective-students/postgraduate/pgr/how-to-apply

If you would like us to consider you for one of our scholarships you must apply by 12 noon on the 5th December 2016 at the latest.

References

Foti R. et al., Nuclear architecture organized by Rif1 underpins the Replication-timing program,. Mol Cell. 2016 Jan 21;61(2):260-73.

Sukackaite, Structural and biophysical characterization of murine Rif1 C-terminus reveals high specificity for DNA cruciform structures. J Biol Chem. 2014 May 16;289(20):13903-

Cornacchia D et al., Mouse Rif1 is a key regulator of the DNA replication-timing program in mammalian cells, EMBO J. 2012 Sep 12;31(18):3678-90.

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