PhD position in biochemistry of DNA mismatch repair: Coordination of DNA mismatch repair by multiple state machines

Job description

DNA mismatch repair is important for maintaining genome stability through repair of DNA replication errors. Non-functional mismatch repair results in a mutator phenotype and in humans increases the risk to develop cancer. Mismatch repair involves the coordinated action of multiple proteins, amongst which MutS and MutL (in prokaryotes) and MutSα and MutLα (in eukaryotes) that recognize the replication error. In this project you will study how the complete MMR reaction is coordinated by multiple state machines.

Specifically, you will aim to find out how:

• the MutS/MutSα and MutL/MutLα ATPases coordinate repair and
• how directionality is achieved.

You will achieve this through using mutant and obligate asymmetric bacterial MMR repair proteins in our reconstituted E.coli MMR assay. You will purify human MMR proteins (with NKI, Amsterdam) and reconstitute the human MMR reaction so that analogies and differences with the bacterial system can be studied in detail. In collaboration with other consortium partners, you may then explore the actions of individual molecules on DNA in different reaction substeps using in vitro or in vivo single molecule approaches (CNRS Paris, Chalmers University Sweden, or Oxford University UK).

Work environment

This position is part of the Doctoral Training Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector. You will be immersed in an international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes. As the research relies on cutting-edge technologies, development of new approaches will be an integral part of your project. Training includes one or more rotations within European partner laboratories. Through collaboration with industry, you will learn how technology development drives innovation in research. In addition, you will learn how to disseminate and communicate your project in close collaboration with the creative sector.

For this project you will be employed by Erasmus MC. This is the largest academic hospital in The Netherlands and strives towards a healthy population and excellence in healthcare through research and education. The Department of Molecular Genetics is well known within the field of DNA repair for its competitive international research, which spans the experimental range from animal models to single molecule imaging. Our research group focuses on biochemical and enzymatic approaches to understand the mechanisms of complex genome transactions such as DNA mismatch repair and the regulation of homeologous recombination at the molecular level.
 

Qualifications and skills

We are looking for an enthusiastic candidate with a MSc in Biochemistry, Structural Biology or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities.

There are strict eligibility requirements for the PhD positions in MSCA-DN:

• Applicants should not have resided or performed their main activity (work, studies, etcetera) in the Netherlands for more than 12 months in the 3 year period immediately prior to the start date of this position.
• Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).

Before you apply please check our conditions for employment.

Terms of employment

• You will receive a temporary position for 4 years. The gross monthly salary is € 2.789 ,- in the 1st year and increases to € 3.536 ,- in the 4th year (scale OIO).
• Excellent fringe benefits, such as a 13th month that is already paid out in November and a individual travel expense package.
• Pension insurance with ABP. We take care of approximately 2/3 of the monthly contribution.
• Special benefits, such as a incompany physiotherapist and bicycle repairer. And there is also a gym where you can work on your fitness after work.

Additionally, employment terms for Marie Curie projects apply for the first 3 years of employment.
 

More information

• For more information on the RepState training network, see www.repstate.eu.
• For more information about this position at Erasmus MC, please contact Dr. ir. Joyce Lebbink (j.lebbink@erasmusmc.nl).

If you are excited by the thought of this position and would like to apply, please do so by using the application form on our website. Applications should include:

• a cover letter explaining why you are interested in the project,
• resume (CV),
• contact info for two referees.
• detailed academic transcripts.

Application deadline is April 9th 2023. Note that multiple positions are open within this project, and applications to multiple projects are welcome. Details on other project vacancies are available on www.repstate.eu.

For the purposes of confirming eligibility, all applications will be shared with the RepState management team.

No agencies please.