cellular stress response in the nervous system

Cells exhibit diverse responses to ionizing radiation (IR), ranging from activating survival pathways to inducing apoptosis, which is utilized in radiotherapy to eliminate cancer cells. The cellular response to IR is influenced by the cell type involved, with varying degrees of resistance observed. The radioresistance of tumor cells often stems from the inherent radioresistance of the cell type from which the tumor originates. However, limited knowledge exists regarding the radiosensitivity of untransformed glial cells in mammalian models due to challenges in culturing these cell types.

Research conducted in our laboratory using Drosophila melanogaster as a model system has provided insights into the intrinsic mechanisms of normal glial cells that dampen the apoptotic response following irradiation. These findings suggest that such mechanisms could contribute to the radioresistance observed in glioma cells. Remarkably, some of the mechanisms identified in human glioma cells, such as the impaired ability of p53 to induce apoptosis after irradiation, also operate in normal glial cells, thereby reducing their radiosensitivity.

Objective and Approach: This proposal aims to identify the molecular factors that either prevent or attenuate the apoptotic response in glial cells following radiation exposure. To achieve this goal, our research will concentrate on the highly advantageous and genetically tractable model organism, Drosophila melanogaster. By utilizing this system, we intend to unravel the molecular network underlying the intrinsic resistance of glial cells to radiation. Subsequently, we will formulate specific hypotheses regarding the mechanisms conferring radioresistance to gliomas in Drosophila.