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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:
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).
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.
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:
Before you apply please check our conditions for employment.
Additionally, employment terms for Marie Curie projects apply for the first 3 years of employment.
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:
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.
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You have been invited for an interview, great! In this first meeting we get to know each other and see if You can form an idea of the position, the department and Erasmus MC. If the interview goes well usually a second interview follows.
It’s a match! Your future manager will discuss your salary and employment with you. You will also receive more information about our other terms of employment.
Your first working day has come! We are more than happy to have you. Your new department will give you a warm welcome and provide you with all the information you need. Enjoy your job at Erasmus MC!
Erasmus MC is an international leading academic hospital in Rotterdam. We are recognized as a world-class scientific research organization aiming to improve our understanding of diseases and disorders and helps to predict, treat and prevent them. We have access to the latest equipment and techniques. A working environment that gets the best out of people.Find out more about Erasmus MC