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Molecular mechanisms of eukaryotic SMC complexes

MRC London Institute of Medical Sciences (LMS)

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Dr L Aragon No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

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 fibres. 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.

The group 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/biophysical and in vivo characterization of the molecular mechanisms of distinct SMC complexes as well as their regulation and function on chromatin.

Candidates should be highly motivated, committed and have clear career goals. Interest in biochemistry (protein purification/structural analysis) and biophysics (single molecule assays) as well as cell biology and genetics will be important.

To Apply: Please visit our website ( to download an application form.

Funding Notes

This project is one of multiple available projects potentially funded by the MRC. If successful the studentship would cover all tuition fee payments and includes a tax-free stipend amounting to £21,000pa (paid in monthly installments directly to the student) for 3.5 years.

This direct funding is available for UK/EU students only.
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