10/01/2017

PHOSPHATASE-DIRECTED TARGETING OF THE DNA-REPAIR CAPACITY IN CANCER


  • OFFER DEADLINE
    09/04/2017 13:30 - Europe/Athens
  • LOCATION
    Belgium, Leuven
  • ORGANISATION/COMPANY
    KU Leuven

(Ref. BAP-2017-3)

Tewerkstelling : Voltijds

Duur : Bepaalde duur

Plaats : Leuven

Solliciteren tot en met : 09/04/2017

For the Laboratory of Biosignaling & Therapeutics we are looking for a highly motivated PhD student

PHOSPHATASE-DIRECTED TARGETING OF THE DNA-REPAIR CAPACITY IN CANCER

The Laboratory of Biosignaling & Therapeutics investigates cellular signal transduction pathways at the molecular level. A major current goal is to develop protein phosphatase PP1 as a target for novel cancer and neurodegeneration therapies.

Website unit

Project

Research project

Cells have evolved elaborate sensing and repair mechanisms to deal with various types of DNA damage. We have found that the deletion of NIPP1, a substrate-targeting subunit of protein phosphatase PP1, dramatically increases the DNA-repair capacity. Conversely, the overexpression of PP1-NIPP1 in human cells induces numerous DNA lesions. Here, we propose to study the molecular mechanism(s) by which PP1-NIPP1 reduces the DNA-repair capacity and to examine whether the activation of PP1-NIPP1 has therapeutic potential. First, knockout and overexpression models will be used to examine which DNA-repair pathways are regulated by PP1-NIPP1. Next, we will identify the DNA-repair substrates of PP1-NIPP1, using two novel substrate-mapping methods, and explore how their dephosphorylation affects the expression, targeting, and activity of specific DNA-repair factors. We will also engineer cells to allow the inducible activation of endogenous PP1-NIPP1 and examine whether this causes cell death in immortalized cells, before and after their oncogenic transformation. Finally, we will perform a screening for small-molecules that interfere with the interaction between PP1 and a PP1-inhibitory domain of NIPP1 and are predicted to activate PP1-NIPP1. These compounds will be tested for their effects on the viability of a broad panel of cancer cells. This project is expected to yield novel insights into the regulation of the DNA-repair capacity that can be exploited therapeutically.

Profile

  • You have a good background in basic sciences.
  • You are willing to learn and adopt a variety of techniques of biochemistry, molecular biology and cell biology.
  • You have excellent oral and written communication skills, and have a good knowledge of English.
  • You aim for perfection and are practically skillful.
  • You are ambitious, inventive and have a long-term vision.
  • You are willing and capable to work as a team member.

Offer

  • We offer a doctoral position for 4-5 years in a stimulating scientific environment.
  • You will be registered in specific program of the doctoral school and will be able to attend the associated courses.
  • You will have access to state-of-the-art research facilities.
  • You will be guided on a daily basis by well-trained professionals and get a thorough training in scientific thinking, practice, presentation and writing.

Interested?

For more information please contact Prof. dr. Mathieu Bollen, tel.: +32 16 33 06 44, mail: mathieu.bollen@kuleuven.be.

You can apply for this job no later than April 09, 2017 via the online application tool