{"id":1420,"date":"2021-04-09T12:21:44","date_gmt":"2021-04-09T12:21:44","guid":{"rendered":"https:\/\/www.ivb.ro\/?page_id=1420"},"modified":"2021-04-09T12:32:05","modified_gmt":"2021-04-09T12:32:05","slug":"radiobiologie-project-eli-09","status":"publish","type":"page","link":"https:\/\/www.ivb.ro\/en\/radiobiologie-project-eli-09","title":{"rendered":"Radiobiologie – Project ELI-09"},"content":{"rendered":"
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\n\t\t\t\t\t\tAdvanced biological methods for investigating the stress responses of normal and pre-leukemic cells under irradiation at ELI-NP, \u2013 applications for astrobiology, and the FLASH radiotherapy \/ CELLI \t\t\t\t\t<\/p>\n\t\t\t\t\n\t\t\t<\/div>\n\t\t\t\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Project ELI-09<\/strong><\/span><\/p>

Advanced biological methods for investigating the stress responses of normal and pre-leukemic cells under irradiation at ELI-NP, \u2013 applications for astrobiology, and the FLASH radiotherapy \/ CELLI <\/strong><\/span><\/p>

PROGRAM<\/strong><\/span><\/p>

PNCDI 3, Program 5 \u2013 Research in strategic domains, Sub-program 5.1 The research, development and innovation program for technologies in the field of ultra-power lasers \u2013 ELI-RO. Project type: R&D.<\/span><\/p>

Place of the project in the framework\/context of the ELI-NP White Book <\/strong><\/span><\/p>

LGE\/III.5 Biological systems under irradiation<\/span><\/p>

TDR4 topic 2.6. Biological systems under irradiation<\/span><\/p>

Project duration<\/strong><\/span><\/p>

01.10.2020 \u2013 30.09.2023<\/strong><\/span><\/p>

Consortium<\/strong><\/span><\/p>

Coordinator <\/strong><\/span><\/p>

\u201d<\/strong>Victor Babe\u0219\u201d National Institute of Pathology, Bucharest, ROMANIA (IVB)<\/span><\/p>

Project directorDr. Gina MANDA<\/span><\/p>

Partner 1 <\/strong><\/span><\/p>

\u201cHoria Hulubei\u201d National Institute for R&D in Physics and Nuclear Engineering, M\u0103gurele, ROMANIA (IFIN-HH)<\/span><\/p>

Project responsible: Dr. Andi Sebastian Cucoanes<\/span><\/p>

Budget<\/strong><\/span><\/p>

1,000,000.00 Lei<\/strong><\/span><\/p>

Useful links<\/strong><\/span><\/p>

ELI-RO IFA http:\/\/www.ifa-mg.ro\/eli\/<\/a><\/span><\/p>

ELI \u2013NP http:\/\/www.eli-np.ro\/<\/a><\/span><\/p>

\u201cVictor Babe\u0219\u201d National Institute of Pathology https:\/\/www.ivb.ro\/v3\/ro\/<\/a><\/span><\/p>

\u201cHoria Hulubei\u201d National Institute for R&D in Physics and Nuclear Engineering https:\/\/www.nipne.ro\/<\/a><\/span><\/p>

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Project Summary<\/strong><\/span><\/p>

Background<\/strong>: <\/strong>An important objective of ELI-NP is to demonstrate the biological effects of the laser-generated pulsed multi-energetic ionizing radiations using cells under irradiation (LGE\/III.5, TDR4). The proposed radiobiology experiments are designed to bring original contributions in the field of astrobiology and radiotherapy. Astrobiology investigations in the context of ELI-NP were initiated by the coordinator of the present project (IVB) in the previous Eli-RO project (13-ELI\/2016) through which a dedicated biomedical platform was built, as well as the prototype of the irradiation cassette for exposing cells in the E5 area at ELI-NP. Moreover, preliminary results were obtained to demonstrate our innovative biomedical strategy for investigating proliferating monocytes under irradiation using available continuous<\/em> radiations. The study was mainly\u00a0 financed by ELI-RO and had the logistic support of European Space Agency (ESA) and GSI Center for Heavy Ion Research (Germany) through the AO-2017-IBER program financed by ESA.<\/span><\/p>

Main project objective<\/strong>: <\/strong>to enlarge the portfolio of advanced biological investigations addressing the interaction of cells with radiation, relevant for astrobiology and FLASH radiotherapy studies at ELI-NP.<\/span><\/p>

Scientific objectives<\/strong>:<\/span><\/p>

(1)<\/strong> To implement the concept of \u201cnetwork medicine\u201d at ELI-NP for understanding the mechanisms underlying the response of normal and pre-leukemic cells exposed to pulsed, multi-energetic radiations produced at ELI-NP, as compared to conventional continuous radiations;<\/span><\/p>

(2)<\/strong> To sustain this network approach by advanced biomedical in-vitro<\/em> methods that will be used for preliminary experiments at ELI-NP: metabolomic investigations using hyperpolarized nuclear magnetic resonance; reactive oxygen species measurements using electron paramegnetic resonance; functional and transcriptomic investigations using multi-color flow cytometry and pathway-focused PCR arrays;<\/span><\/p>

(3)<\/strong> Integration of data in biologic networks for highlighting the potentially unique biological effects of the radiations generated at ELI-NP.<\/span><\/p>

Technologic objectives<\/strong>:<\/span><\/p>

(1)<\/strong> Design of experiments regarding the interaction of cells with radiation generated by high-power lasers;<\/span><\/p>

(2)<\/strong> Design and fabrication of cells holders and their integration into the irradiation installations at ELI-NP and IFIN-HH;<\/span><\/p>

(3)<\/strong> Development of the biology laboratory built at ELI-NP;<\/span><\/p>

(4)<\/strong> Setup of a project-dedicated biobank at ELI-NP; (5)<\/strong> First biologic experiments at ELI-NP using electron and proton beams; (6)<\/strong> knowledge and technology transfer to ELI-NP.<\/span><\/p>

Secondary objectives<\/strong>:<\/span><\/p>

(1)<\/strong> Strengthening of the multi-disciplinary consortium built in the 13-ELI project, by increasing its competence and by recruiting young researchers;<\/span><\/p>

(2)<\/strong> Generation of scientific and technical knowledge within the consortium regarding the investigation of cells under irradiation;<\/span><\/p>

(3)<\/strong> Increase of the international visibility of ELI-NP and its partners by publications and communications in highly ranked journals and conferences;<\/span><\/p>

(4)<\/strong> development of international collaborations for submitting large-scale projects.<\/span><\/p>

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Multi-disciplinary consortium<\/strong>: <\/strong>\u201dVictor Babes\u201d National Institute of Pathology (coordinator, IVB) and \u201eHoria Hulubei\u201d National Institute for Physics and Nuclear Engineering (partner, IFIN-HH), which has as its main core a team from ELI-NP. The consortium joins expertise in the fields of physics, biophysics, biology, biochemistry and radiochemistry. Most of the team members have collaborated since 2014 for elaborating TDR4 and thereafter in the frame of the 13-ELI project (ELI-RO).<\/span><\/p>

Expected results<\/strong>: <\/strong><\/span><\/p>

(1) <\/strong>Customized cells holders for irradiation at Eli-NP;<\/span><\/p>

(2)<\/strong> Tritium-labelled biomolecules (\u22653);<\/span><\/p>

(3)<\/strong> panel of biomarkers specific for cellular responses to radiation; (<\/strong><\/span><\/p>

4)<\/strong> Technology transfer protocol towards ELI-NP, including operational procedures and technical reports;<\/span><\/p>

(5)<\/strong> Biobank at ELI-NP;<\/span><\/p>

(6)<\/strong>\u00a0 Publications (\u22654) and communications (\u22658);<\/span><\/p>

\u00a0(7)<\/strong> Workshops (2);<\/span><\/p>

(8)<\/strong> Summer school;<\/span><\/p>

(9)<\/strong> Astrobiology project proposal to the AO-IBER program for continuing the collaboration with ESA and GSI;<\/span><\/p>

(10)<\/strong> PhD thesis (synchronisation and coherent<\/span><\/p>

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OUTLINE OF THE MAIN TASKS<\/strong><\/span><\/p>

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International collaboration<\/strong><\/span><\/p>

IV<\/strong><\/span><\/p>

Astrobiology<\/em><\/strong><\/span><\/p>

The IVB team is involved in astrobiology through the project \u201cRedox signalling and the transcription factor NRF2 as therapeutic target for counteracting the deleterious effects of spaceflight environment\u201d, 2018-2021. The project is financed by the European Space Agency through the Programme INVESTIGATIONS INTO BIOLOGICAL EFFECTS OF RADIATION USING THE GSI ACCELERATOR FACILITY (AO-2017-IBER). In this project we are specifically collaborating with Dr. Nicole Averbeck and Dr. Ulrich Weber from GSI Helmholtz Center for Heavy Ion Research (Darmstadt, Germany), as well as with the . iEuropean biophysics group established through the above mentioned Programme.<\/span><\/p>

Redox biology<\/em><\/strong><\/span><\/p>

1)<\/strong> Collaboration with the EU-ROS consortium (http:\/\/eu-ros.eu\/);<\/span><\/p>

2)<\/strong> Collaboration with Prof. Antonio Cuadrado from the Autonomous University of Madrid, Spain in the field of the transcription factor Nrf2 which is critically involved in the activation of the antioxidant response and may be a valuable drug target for modulating oxidative stress in pathological conditions, including exposure to ionizing radiation. Prof. Cuadrado is coordinating the project \u201cKnowledge transfer in redox biology for developing advanced molecular tools in neurodegenerative diseases \u2013 focus on the signature of NRF2 transcription factor in diagnosis and therapy\u201d, acronym REDBRAIN, project ID P_37_732, 2016-2021, financed by European Funds for Regional Development through the Competitiveness Operational Program 2014-2020, that is currently implemented in IVB. Moreover, we were partners with Prof. Cuadrado in the M-Era.Net project NANOTHER (2016-2019).<\/span><\/p>

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ELI-NP<\/strong><\/span><\/p>

The Biophysics and Biomedical Applications Laboratory, representing the main ELI-NP structure involved in the project, developed collaborations with a several institutions from Romania and abroad, in various research directions, in the fields of radiobiology, hyperpolarized spectroscopy and NMR methods such as: Molecular imaging of radiation effects, metabolic networks involved in the cellular response to radiation; New biomarkers for radiation effects;\u00a0 Free-radical generation effects of radiation in water and HDO as a nuclear spin polarisation source for biomarkers; Magnetic resonance methods for biomarker follow-up.<\/span><\/p>

The collaborations include Laboratoire des BioMol\u00e9cules of \u00c9cole normale sup\u00e9rieure Paris, Institute of Biological Chemistry of Vienna University, and also Romanian institutions such as Research Institute and the Faculty of Chemistry, both of the University of Bucharest, Institute of Organic Chemistry of the Romanian Academy, Amethyst Radiotherapy Clinic, and Carol Davila University of Medicine and Pharmacy. Support programs: the National Core Program, Fundamental Research Program, \u201cExperimental – Demonstrative Project\u201d program. The research program of ELI-NP includes also the study of biological systems under irradiation at E4 and E5 Experimental areas. This direction belongs to the broader field: \u201cEvaluation of cosmic stressors effects in materials, electronic devices and biological systems\u201d and it is described in TDR4. The biophysics related part has been developed in close collaboration with \u201eVictor Babes\u201d National Institute of Pathology, however the collaboration is broader and includes GSI Helmholtz Centre for Heavy Ion Research, National Institute for Laser, Plasma and Radiation Physics Romania, University of Bucharest, West University Timisoara, Romania and Queen’s University Belfast. Support programs: Core Program, Space Technology and Advanced Research Program (STAR).<\/span><\/p>

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IFIN-HH<\/strong><\/span><\/p>

The IFIN-HH\/DRMR team develops research activities in the field of ionising radiation dosimetry in cooperation with Laboratoire National Henri Becquerel (LNHB) – CEA Saclay France, University of Bucharest-Faculty of Physics (Absorbed dose simulation, developing of new dosimetry systems; treatability of dosimetry measurements). Support programs: the national Core Program, the IFA CEA Program.<\/span><\/p>

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COST proposals in the field of CELLI submitted to the 2020 Call<\/strong><\/span><\/p>