Super-resolved analysis of lamin-mediated DNA damage repair after high LET irradiation and its applicability to predictive modelling of individual radiation sensitivity in cancer patients
Particle therapy is a promising treatment for patients with solid tumors near sensitive organs or radiation-resistant tumors. However, the induced DNA damage is complex and not well understood, precluding reliable biodosimetry in terms of individual radiation sensitivity. And while microscopy is the gold standard for gauging the level of DNA damage at the single cell level, conventional techniques fail to unravel the exact nature and composition of these clusters. We propose to use fluctuation-enhanced expansion microscopy to gain super-resolved insight in DNA damage clusters. We intend to exploit this technology to quantitatively investigate DNA damage repair pathways and kinetics after exposure to proton and carbon ion irradiation. We will hereby specifically focus on the role of nuclear lamins, as they regulate nuclear architecture, DNA damage repair and mutations in their encoding genes predispose for accelerated aging disease and cancer. To do so, we will exploit a panel of genome-edited cell lines that are depleted from each lamin subtype (A/C,B1,B2) or a crucial processing enzyme (ZMPSTE24) thereof. Using this highly relevant biological use-case, we expect this work to provide a much more quantitative insight in DNA damage and repair after high LET radiation. This should in turn help build better predictive biophysical models that aid in clinical treatment planning based on patient’s individual radiation sensitivity.
The minimum diploma level of the candidate needs to be
- Master of sciences
- Master of sciences in engineering
- Master of industrial sciences
The candidate needs to have a background in