Postdoc in DNA replication (London, UK)

The DNA replication group, Imperial College London, is looking to recruit a postdoctoral researcher interested in cutting edge DNA replication research.

Duplication of the genome is an extraordinarily complex process, involving a large number of enzymes and an intricate regulatory network to promote faithful DNA replication. Errors during DNA replication have far reaching consequences and are responsible for several diseases, most notably cancer. The complexity of the DNA replication machinery means that only now we are beginning to understand how individual proteins promote replisome assembly and DNA replication.*Description:*

Our goal is to understand the mechanisms that promote accurate

function of the DNA replication machine, as this represents the basis

for genomic stability and life itself. We have recently developed a

reconstituted system that recapitulates initiation of DNA replication

in vitro, which proofed to be very successful in identifying crucial

mechanism in the loading and activation of the replicative helicase

(Fernandez-Cid et al Mol Cell, Sun et al Nature Structure & Molecular

Biology, Samel et al Genes & Dev, Evrin et al PNAS…). The candidate

will employ this well-established system to discover new functions of

DNA replication proteins, to identify novel replication factors, to

determine the structures of large DNA-protein complexes using electron

microscopy and cross-linking / mass spectrometry and the dynamics of

replication factors in collaboration with specialized groups. We

employ Saccharomyces cerevisiae, which is the most used model system

to study DNA replication, as replication factors are well conserved

between yeast and humans and yeast is readily amendable to genetic and

biochemical interrogations. This position will offer the candidate

significant training opportunities, the chance to develop personally

and professionally, a stimulating research environment and deep

insights into DNA replication and genome stability.


*Your qualifications:* PhD

*Position:* The post is initially funded for one year with possibility

for extension for up to 4 years.

*Research fields:* Biochemistry, Molecular Biology, Structural Biology,

Single-Molecule Experience, Electron Microscopy


*We offer:*

• The possibility to work on a cutting-edge project using state-of-

the-art technology in a highly motivated research team

• A stimulating, diverse and international research environment

• Advanced training opportunities, special seminar programs,

tutorials on grant writing and career development


Please send your application with the relevant documentation (CV,

letter of motivation and two references) by email to:

christian.speck@imperial.ac.uk


*For more information on the group visit:*

www.imperial.ac.uk/people/chris.speck

http://www.specklab.com/


*References:*


Samel AS, Fernández-Cid A, Riera A, Tognetti S, Herrera MC, Speck C

(2014). A unique DNA entry gate for regulated loading of the

eukaryotic replicative helicase onto DNA. *Genes & Development*, Aug

28:1653-1666


Fernández-Cid A, Riera A, Tognetti S, Herrera MC, Samel S , Evrin C,

Winkler C, Gardenal E, Uhle S, Speck C. (2013). An ORC/Cdc6/MCM2-7

complex is formed in a multistep reaction to serve as a platform for

MCM2-7 double-hexamer formation. *Molecular Cell*, Volume 50, Issue 4,

577-588, 18 April


Sun J, Evrin C, Samel S, Fernández-Cid A, Riera A, Kawakami H,

Stillman B#, Speck C#, Li H# (2013). Architecture of the eukaryotic

replication-licensing complex OCCM formed by ORC-Cdc6 and Cdt1-MCM2-7

on DNA.* Nature Structure & Molecular Biology*, August 5, (20), 944

–951. # Corresponding author


Evrin C, Fernández-Cid A, Zech J, Herrera MC, Riera A, Clarke P, Brill

S, Lurz R, Speck C. (2012). In the absence of ATPase activity, pre-RC

formation is blocked prior to MCM2-7 hexamer dimerization. *Nucleic Acids Research*, Mar 1;41(5):3162-72


Evrin, C., Clarke, P., Zech, J., Lurz, R., Sun, J., Uhle, S., Li, H.,

Stillman, B., Speck, C. (2009). A double-hexameric MCM2-7 complex is

loaded onto origin DNA during licensing of eukaryotic DNA replication.

*PNAS* 106, 20240-20245