Radiobiology – AO-2017-IBER (ESA-HRE-UL-LE-0003)

Financing authority: European space agency through the AO-2017-IBER programme (INVESTIGATIONS INTO BIOLOGICAL EFFECTS OF RADIATION USING THE GSI ACCELERATOR FACILITY)

Coordinator: Gina Manda, “Victor Babes” National Institute of Pathology, Romania

Partner: GSI Helmholtz Centre for Heavy Ion Research, Germany

Duration: 2017-2021

Abstract

Aim: 1) to investigate by functional genomics the redox signalling network in human immune-relevant cells exposed to ionizing radiation in experimental settings that mimic on-ground the exposure of astronauts to galactic cosmic rays (electrons, protons and 12-C); 2) to demonstrate in vitro that pharmacologic modulation of the transcription factor NRF2, which is critically involved in cytoprotection against oxidative and electrophilic stress , could provide to astronauts protection against the aggression of the spaceflight environment and to its short- and long-term health consequences.

AO-2017-IBER topic: A1 Understand how cellular radiation response is affected by spaceflight environment, and Identify targets for therapeutic intervention; A4 Develop mitigation measures for radiation effects, including biomedical counter measures.

Supporting project: Development of the national technological platform for investigating the interaction of complex biological systems with space radiations in the context of ELI-NP” – Astro-Bio-ELI, financed by the Romanian Ministry of Research and Innovation, ELI-RO IFA program, grant 13 ELI/2016, 2016 – 2019. ELI-NP is part of the pan-European research project Extreme Light Infrastructure which is under construction in Romania. It will be the most advanced research facility in the world, focusing on photonuclear physics, comprising a very high intensity laser of two 10 PW ultra-short pulse lasers and the most brilliant tunable gamma-ray beam. This will enable ELI-NP to tackle a wide range of research topics, including astrobiology.

Innovation

• Comprehensive molecular study on oxidative stress and antioxidant responses in monocytes exposed to space-relevant radiation;
• Highlighting of the transcription factor NRF2 as potential therapeutic target for counteracting the deleterious action of ionizing radiation;
• Preparation of molecular studies for investing the unique multi-component and multi-energetic radiation that is expected to be generated at ELI-NP.

Expected results

1. a) the molecular profile of monocytes (cell lines and primary cells) irradiated with electron, proton and 12-C beams, and its evolution registered every 24 hrs for at least 72 hrs post-irradiation;
2. b) the involvement of the NRF2 transcription factor in cellular responses of irradiated monocytes/macrophages evaluated as molecular fingerprint (expression of genes that are under NRF2 control); c) the modulatory effect exerted in vitro by pharmacologically approved NRF2 activators (like SFN or DMF) on the molecular profile of irradiated monocytes; in vitro proof-of-concept for NRF2 activators as potential therapeutic agents for counteracting the deleterious effects of ionizing radiation in irradiation settings relevant for exposure of astronauts to space environment.

Results obtained using the irradiation facilities of GSI will be correlated with those obtained at Romanian facilities in the frame of the Astro-Bio-ELI project (gamma/X rays and electron beams, possibly proton beams). Hence, inter-comparisons will be made that will considerably increase confidence in the obtained results and will further guide our studies. Most important, a large set of data will be generated for characterizing in vitro the response of monocytes to various types ionizing radiation at doses / dose rates relevant for the space exposure (doses lower, bellow 1 Gy) and for cancer therapy (higher doses, above 2 Gy).