Hyperthermia (HT) - temporary elevation of tumor temperature to 41-43 °C - inhibits repair of DNA double-strand breaks (DSBs) by targeting the BRCA2 protein, making it a powerful radio- and chemosensitizer with proven clinical track record. However, the efficacy of HT treatments can be negatively affected by insufficient thermal dose delivery, temporary nature of HT effects and induction of thermotolerance (temporary resistance to subsequent HT treatments). Recently, we found that inhibition of the chaperone HSP90 enhances the effects of HT treatments in vitro, without affecting non-heated cells, establishing it as a straightforward, safe and efficient approach to improve HT treatment efficacy.

In the first phase of the current project, the candidate will optimize the treatment protocols for enhanced radio/ chemo-sensitization and reduced thermotolerance induction in vitro and extend them to cell lines derived from cancer of breast, bladder, head & neck and melanoma. In the second stage, the candidate will determine the effect of HSP90i on the BRCA2 proteome using mass spectroscopy. Positive results of this project studies can enable fast clinical introduction of HSP90i-assisted hyperthermic anticancer therapies.

We are looking for a hard-working, flexible, independent and motivated candidate holding a MSc degree in Biomedical Sciences (or equivalent), with ample research experience in (molecular) cell biology, preferably in the fields of oncology and/or mass spectroscopy. Ability to work in a team and excellent verbal and written English skills are a must.

Being able to present a certificate of good conduct is a condition for the appointment.

You will receive a temporary position for 4 years. The gross monthly salary is € 2.279,- in the 1st year and increases to € 2.919,- in the 4th year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC).

Erasmus MC

A healthy population and excellence in healthcare through research and education. This is what Erasmus MC stands for. Conducting groundbreaking work, pushing boundaries and leading the way. In research, education, and healthcare. We are practical people with a high level of expertise, working hard to improve and renew the healthcare of today and the public health of tomorrow.

This project is a collaborative effort between the AMC (group of Dr. P. Krawczyk at the Department of Medical Biology and Dr. N.A. Franken at the Laboratory for Experimental Oncology and Radiotherapy) and Erasmus MC (group of Prof. Roland Kanaar at the Deptartment of Molecular Genetics). The team includes multiple PhD students, postdocs, technicians and senior scientists and is supported by multiple clinicians who facilitate its translational aspects. Both institutes offer access to cutting-edge facilities (animal, mass spectrometry, microscopy, flow-cytometry, CRISPR/Cas cloning and sequencing, among others) and extensive expertise in all technologies required by the project. The PhD student will be appointed at the Department of Molecular Genetics at Erasmus MC.

Within the Department of Molecular Genetics our research group aims to understand fundamental principles that determine complex biological processes. We currently focus on the process of double-strand DNA break repair in relation to genomic (in)stability, carcinogenesis and radio- and chemotherapy. We develop and apply new methods from single molecule imaging to live cell microscopy for quantitative analysis of detailed molecular function. Although our focus is fundamental knowledge, the mechanistic information we reveal are needed both to understand molecular causes that promote tumor formation, and to design of strategies specifically sensitizing rapidly dividing cells to anti-cancer treatments based on DSB induction.