Radiotherapy remains unavoidable in most cancer treatments. However, its effectiveness is accompanied by the side effects due to the irradiation of healthy cells adjacent to cancer cells. Thus, understanding the biological consequences responsible for the damage of healthy tissue is essential for the development of methods to prevent, mitigate and treat toxicity induced by exposure to ionizing radiation.
Skeletal striated muscle, which accounts for up to 40% of body mass, is often included in the treatment field. Although the macroscopic consequences of radiotherapy on the muscle tissue are well studied, little is known about the molecular mechanisms involved in the myonuclei of myogenic cells to maintain a highly coordinated cellular metabolism and muscular tissue homeostasis.

The stage will take place at the Laboratory of Radiobiology of Accidental Exposures (LRAcc) within the Department of Research in Radiobiology and Regenerative Medicine (SERAMED) of the Department of Health of the Institute of Radiation Protection and Nuclear Safety (IRSN).

The goal of this project is to understand how myotubes, polynuclear cells of skeletal muscle tissue, in comparison to its mono-nuclear precursors, myoblasts, maintain their cellular functions when one or more of their nuclei are damaged upon irradiation. Interaction of ionizing radiation with living matter induces various types of damage, particularly at the DNA level, within cell nuclei. Accordingly, eukaryotic cells have developed a set of complex multi-protein systems to signal and repair most of DNA lesions and thus to maintain the genomic integrity and epigenetic regulation. Recent studies showed that the DNA damage response extends beyond the irradiated cells. As we previously observed differential DNA repair response during myogenic differentiation (Sutcu et al, Life Sci Alliance, 2023), the candidate will thus investigate whether cell survival and DNA repair kinetics would be impacted by potential inter and intra-cellular communications within this specific tissue.
To this aim, the candidate will i) work with an in vitro myogenic differentiation model to generate from proliferative myoblasts (mononuclear and proliferative cells) multi-nucleated and post-mitotic myotubes, which have ectopic expression of DNA repair proteins of interest coupled to GFP and ii) use a microscopy integrated system to induce local DNA lesions within one or more myonuclei. The impact of the inter and intra-cellular communications will be assayed by evaluating the treatment with specific DNA repair and cellular communication inhibitors on a) the survival of different myogenic cells upon irradiation at different doses using MTT assay and b) the dynamic behavior of GFP-tagged DNA repair proteins using real-time imaging techniques in the different cell types followed by immune-fluorescent labelling post-fixation.

This internship will allow the selected student to improve his/her technical skills in cell biology and molecular biology, and to learn about immunofluorescence and confocal microscopy techniques. In addition, the candidate will acquire solid knowledge in radiobiology and DNA repair.
We are seeking for highly motivated M2 student in biology / health sciences, with good knowledge in cellular and molecular biology and a strong inclination for microscopy.

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