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PhD candidate ‘Lamin deregulation and nuclear envelope rupture in cancer invasion and metastasis in vivo’

The aim of this project is to test whether and how lamin deregulation contributes to metastatic disease progression in the living organism.

4 maanden geleden

Arbeidsvoorwaarden

Standplaats:
Geert Grooteplein Zuid, Nijmegen, Gelderland
Dienstverband:
Tijdelijk contract / Tijdelijke opdracht
Uren per week:
36 uur
Opleidingsniveau:
WO

Functieomschrijving

In many solid tumors, metastatic progression and poor outcome associate with deregulated nuclear envelope composition, including up- or downregulation of A- and B-type lamins. We have previously identified the cell nucleus as rate-limiting cell organelle that determines the efficacy of tumor cell invasion in vitro, and have mapped lamin A/C and lamin B2 as key regulators of nuclear deformability during altered 3D tissue invasion. Strong nuclear deformation in vitro increases the risk of nuclear envelope (NE) rupture, followed by DNA damage and even fragmentation of the nucleus, and lamin deregulation contributes thus to nuclear damage.

The aim of this project is to test whether and how lamin deregulation contributes to metastatic disease progression in the living organism. Lamin downregulation in particular could enhance cell deformability but also vulnerability of nuclei and DNA damage, thereby directing invasion modes and metastatic efficacy. Using defined solid tumor models of melanoma, sarcoma and breast cancer in vitro and in living mice, the project aims to address the following questions: (1) How are increased or decreased lamin expression levels associated with successful tissue invasion, systemic dissemination and formation of distant metastases? (2) What is the relevance of increased or decreased lamin levels on NE rupture, survival and DNA damage during metastatic progression?

The techniques used in this project comprise the generation and characterization of tumor cell lines of specific lamin expression levels in vitro, intravital tumor imaging in mice by high resolution multiphoton microscopy, and histological analysis of tumor patient samples.

Functie-eisen

The candidate should have a master's degree (or equivalent) in the field of molecular life sciences and a strong interest in studying processes involved in cancer progression.

  • Background in molecular cell biology;
  • Willingness / have experience in working with laboratory animals;
  • High interest and perseverance for mouse intravital microscopic imaging;
  • Completed Article 9 or equivalent (permission to work with laboratory animals) is of advantage;
  • Experience in molecular and cellular techniques, cell culture and microscopy;
  • Motivation, initiative and ambition to publish in high-impact journals;
  • Able to work both independently and in a multidisciplinary team;
  • Excellent communication skills, contributing to a pleasant working atmosphere;
  • High level of proficiency in English;
  • You recognise yourself in the Radboud way of working.

Conditions

Scale 10A: max € 40814 gross per year at full employment (incl. vacation bonus and end of year payments).

Expected start date is July to November 2018.

Read more about the Radboudumc employment conditions.

Additional information

This 4-year-project is funded by the Dutch Cancer Foundation (KWF Kankerbestrijding).

All additional information about the vacancy can be obtained from Dr. Katarina Wolf, assistant professor. Qualified applicants are requested to send a letter describing their interest in the position, qualifications, experience and career goals, as well as a CV and two references.Use the Apply button to submit your application.

Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be a screening based on the provided CV. Radboud university medical center’s HR Department will apply for this certificate on your behalf.