MRC Postdoctoral Research Scientist – Cell Cycle – LMS 1822

MRC London Institute Of Medical Sciences

Description

MRC Postdoctoral Research Scientist

Biochemical and biophysical studies of eukaryotic SMC complexes

(3 Year fixed term)

Salary: £32,302 – £35,143 plus London allowances (£3,727 & £1,402) per annum

London, UK

Every cell contains an enormous amount of DNA organised into one or more chromosomes. Chromosomes need to be accessed by components of the cell so that the information they contain can be read and used. In addition, the integrity of the genetic information must be maintained as cells duplicate, during DNA replication and chromosome segregation. Therefore, from bacteria to mammals, chromosomes require physical manipulation in a manner co-ordinated with cellular activities. To achieve this, cells contain specialised machines that can manipulate chromosome superstructure to ensure that DNA is read, packaged and inherited faithfully. Structural Maintenance of Chromosomes (SMC) complexes are believed to be the machines capable of remodelling chromosome super-structure. Eukaryotes contain three distinct SMC complexes, they are known as Cohesin, Condensin and Smc5/6. They form ring-shaped structures and use ATP hydrolysis to fuel their manipulation in order to change the topology of chromatin fibers. This ability allows SMC complexes to alter local chromatin structure cooperatively to ensure that higher-order manipulation of chromosomes is achieved as required. Although we know some of the functions that the distinct eukaryotic SMC complexes play inside cells, how they work at the molecular level, or even what constitutes their activity is not known.

Our lab has a long-standing interest in studying eukaryotic SMC complexes. For example, we have contributed to understand the role of Condensin in directing Topoisomerase II activity during chromosome segregation (Baxter et al. Science 2011; Leonard et al. Cell Rep 2015; Sen et al. Mol Cell 2016). We have also contributed to identify molecular mechanisms of Smc5/6 function (Bermudez-Lopez et al. Genes Dev 2016) or the involvement of Cohesin in DNA repair (McAleenan et al. Nature 2013) and its regulation by chromatin remodeller complexes (Garcia-Luis et al. Nat StrucMolBiol 2019).

Recently, we used single molecule approaches (optical tweezers and DNA curtains) to demonstrate that purified cohesin complexes tether DNAs in the presence of Scc2/Scc4 and ATP (Gutierrez-Escribano et al. Science Adv 2019) while purified Smc5/6 complexes compact DNA molecules (Gutierrez- Escribano et al. Mol Cell 2020).

We recently succeeded in purifying the three eukaryotic SMC complexes. As a next step we plan to further exploit this and aim to reveal structure-function relationships of SMC complexes.

The successful candidate will have the opportunity to work on several projects related to the biochemical and biophysical characterization of the molecular mechanisms of SMC complexes as well as their regulation and function on chromatin.

Candidates should be highly motivated, committed and have clear career goals. Experience in biochemistry (protein purification/structural analysis) and biophysics (single molecule – optical/magnetic tweezers) is essential, although some training will be provided. All applicants should have a Ph.D. degree in life sciences or equivalent experience and at least one first-author publication published or in press. We offer a highly attractive benefits package including 30 days annual leave plus bank holidays and privilege days, competitive salary and final salary pension scheme along with an interest free season ticket loan.

The LMS is directly funded by the Medical Research Council, and associated with Imperial College. The LMS provide excellent core facilities and support structures, including automated microscopy systems, next generation sequence and proteomics. The Cell Cycle Group is part of the Epigenetics Section and interacts with other groups in the LMS studying cell cycle, cancer, and chromatin organisation.

Salary quoted is inclusive of London weighting. Additional allowances comprise a £1,000 lump sum Settlement Allowance plus a yearly Training Allowance of £850 in the first year, paid in monthly instalments. The Training Allowance increases to £1,300 in year two, and £1,800 in the third year.

This role qualifies for endorsement by UKRI for a UK Global Talent Visa, for which the successful applicant is likely to be eligible to apply. Immigration costs for applicant (100% visa and 100% Health Surcharge) and immediate dependents (100% visa and 50% health surcharge when applying with main applicant) can be reclaimed from LMS after taking up the post (terms and conditions apply).

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