Job description
Correct gene transcription by RNA polymerase II to transcribe new RNA molecules is crucial for proper cell function. However, transcription by RNA polymerases can be blocked by DNA damage, for example by UV-light or other chemicals. This transcription-blocking DNA damage can therefore cause cellular dysfunction and cell death, eventually resulting in DNA damage-induced aging and genome instability. Cells counteract these deleterious effects by transcription-coupled repair (TCR), which…
specifically removes DNA damage in our genes, thereby safeguarding transcription. Our lab has identified several important factors that provided novel insights in this repair pathway (van Sluis et al., Nature Cell Biology 2024; Ramadhin et al., Molecular Cell 2024; van Toorn et al., Molecular Cell, 2022; Geijer et al., Nature Cell Biology, 2021; Tresini et al. Nature, 2015; Schwertman et al. Nature Genetics, 2012).
In this project, we will investigate how mechanical stress affects transcription-coupled repair and transcription stress in differentiated human neurons. Neurons are long-lived, non-dividing cells that depend strongly on continuous and accurate transcription, but they are also exposed to changes in cellular and nuclear mechanics that may interfere with genome stability. Using iPSC-derived neurons, CRISPR-Cas9 gene editing and advanced live-cell imaging, we will investigate how mechanical stress influences transcription stress and transcription-coupled repair, and how defects in these pathways alter the mechanical properties and stress responses of neurons. This project will provide new mechanistic insight into the interplay between mechanical stress, transcription integrity and DNA repair, and may help explain why differentiated neurons are particularly vulnerable during aging and neurodegenerative disease.
Requirements
We are looking for a highly motivated PhD candidate candidate to join the Marie Skłodowska-Curie Doctoral Network NEUROMECH, an international consortium investigating the role of mechanobiology in neurodegenerative diseases. The candidate should have with a MSc. degree in a relevant discipline (e.g. Molecular/Cell biology, Biomedical Sciences, Molecular Sciences, Nanobiology). Experience with the basal transcription process, DNA damage response, Neuronal differentiation systems, live cell imaging is an advantage but not essential. The candidate should be able to independently design, conduct and evaluate research projects, have outstanding theoretical and experimental research skills, is well-organized and result-driven with a strong team spirit. Furthermore, a strong command of (scientific) English in speech and writing is essential (EUR requirements minimum IELTS overall score of 7.0 [comparable to TOEFL PBT: 600; TOEFL CBT: 250; TOEFL IBT: 95]). Being able to present a certificate of good conduct, a valid proof of identity are conditions for the appointment.
Applicants must hold (or expect to obtain before recruitment) a Master's degree or equivalent qualification that entitles them to enroll in a doctoral programme. Candidates must not already hold a doctoral degree at the time of recruitment. In accordance with the Marie Skłodowska-Curie Doctoral Network mobility rule, applicants must not have resided or carried out their main activity (work, studies, etc.) in The Netherlands for more than 12 months during the 36 months immediately preceding the recruitment date, irrespective of nationality. Please ensure that you meet the MSCA eligibility criteria before applying.
Conditions of employment
- You will receive a temporary position for 4 years. The gross monthly salary is € 3.217,- in the 1st year and gradually increases to € 4.077,- in the 4th year (scale OIO).
- A salary increase of 3,5% from May 2027, according to the collective labor agreement (CLA).
- Excellent fringe benefits, such as a 13th month that is already paid out in November and an individual travel expense package.
- An International Office which aids you in preparing for you arrival and stay.
- Pension insurance with ABP. We take care of approximately 2/3 of the monthly contribution.
- Special benefits, such as an incompany physiotherapist and bicycle repairer. And there is also a gym where you can work on your fitness after work.
Employer
Erasmus MC
The department of Molecular Genetics at the Erasmus MC (https://www.erasmusmc.nl/en/research/departments/molecular-genetics) has a strong world-wide reputation in understanding the DNA damage responses at the molecular, cellular and physiological level. The department consists of a vibrant and international group of more than 80 researchers working on various aspects of DNA damage, DNA repair and other DNA damage-related responses. This project will be carried out in the Marteijn lab (www.genomestability.nl) at the Erasmus MC within the Marie Skłodowska-Curie Doctoral Network NEUROMECH (https://neuromech.eu/), an international consortium investigating the role of mechanobiology in neurodegenerative diseases. The Marteijn lab studies the molecular mechanisms how cells deal with DNA damage that interferes with transcription, using a multidisciplinary approach using molecular and cell biological approaches. Our lab works in a highly collaborative manner with a strong focus on state-of-the-art live-cell imaging, genetic and proteomic tools. Our group acts internationally at the forefront of DNA damage and transcription stress. We offer a dynamic, challenging, and cooperative research environment and an excellent training and supervision platform through the PhD teaching program of our Erasmus MC graduate school (https://www.erasmusmc.nl/nl-nl/graduate-school).
The Erasmus MC stands for a healthy population and excellence in healthcare. By conducting groundbreaking work, we aim to push boundaries through leading the way in research, education and healthcare to improve and renew the healthcare of today and the public health of tomorrow. To stimulate research, the Erasmus MC provides access to the latest equipment and techniques in a state-of-the-art environment.
Additional information
For more information about this position, please contact Dr. Jurgen Marteijn, phone number: +31 10 7038169 or e-mail: J.Marteijn@ErasmusMC.nl. For more information visit www.genomestability.nl.
Working at Erasmus MC
At Erasmus MC we dare to step forward in research, education and health care.
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