Start in : January 2021
Duration : 18 month
Workplace : CEA site in Cadarache (Bouches du Rhône, France). A few business trips are to be expected in France and abroad.
IRSN's missions are divided into three areas of expertise: nuclear safety; defense, security and non-proliferation; and environmental health. The Health and Environment Unit includes two departments. The first, dedicated to health, is for medical, health and emergency purposes; the second deals with issues related to the environment, its monitoring and radioactive waste.
Within the Health Department and the Dosimetry Research Service (SDOS), the Microirradiation, Neutron Metrology and Dosimetry Laboratory (LMDN) is equipped with the MIRCOM micro-irradiation platform, which offers the possibility of delivering a predetermined number of ions with defined characteristics (type and energy) to a specific area of the cells, nucleus or cytoplasm, with a spatial resolution around one micron. This platform thus makes it possible to study the links between initial subcellular damage, related to the transfer of energy from ionizing radiation at the cellular level, and its early and later biological effects.
The proposed post-doctoral topic is part of the optimization of micro-irradiation of biological samples on the MIRCOM microbeam. Equipped with a horizontal beam, the microbeam allows targeting adherent cells, such as fibroblasts or endothelial cells. However, the irradiation of other sample types such as non-adherent cells or multi-cellular organisms can become complex due to difficulties in immobilizing the sample. In order to expand MIRCOM's micro-irradiation capabilities, a microfluidic system will be developed that allows the immobilization of several types of samples while maintaining rapid and repeatable micro-irradiation.
The proposed post is an 18-month postdoctoral contract to design and implement such a microfluidic system for the irradiation of microscopic multicellular organisms such as the nematode worm Caenorhabditis elegans and non-adherent cells. This system will then be applied to the study of the ionizing radiation effects on Parkinson's disease. The mechanisms of induction of Parkinson's disease are not fully understood but studies indicate that there may be an increased risk of this disease when exposed to ionizing radiation.
Experimental approach :
The work of the post-doctoral candidate will first consist in developing a microfluidic system adapted to the MIRCOM microbeam, which can be based on existing systems (Keil et al., 2017; Buonanno et al., 2013; Suzuki et al., 2018; Garty et al., 2011). It will propose a tool with sufficient versatility to treat multicellular organisms such as C. elegans or non-adherent cells.
The candidate will then have to perform a characterization of the energy deposit and the microbeam targeting accuracy, while verifying that the microfluidic system does not affect the worms' or cells' physiology. The number of ions passing through the ultra-thin microfluidic chip will be evaluated using the CR-39 ion trace detector placed under the microfluidic chip. This detector will measure the scattering of the ion beam due to the passage of ions through the different layers of materials before reaching the biological sample. The compatibility of this system with the normal maintenance of the physiological functions of biological samples will be evaluated by analyzing dopaminergic neurons specific behaviors such as feeding or chemotaxis behaviors on the one hand, and cell survival on the other hand.
C. elegans Irradiation :
The candidate will be asked to test the microfluidic systems performance on C. elegans in the context of a study of ionizing radiation effects on Parkinson's disease. This disease involves a progressive degeneration of dopaminergic neurons in an area of the brain related to voluntary motor functions.
C. elegans has 8 dopaminergic neurons, which will be specifically targeted using the microbeam. The candidate will propose to perform different measurements to analyze the effect of ionizing radiation on these dopaminergic neurons (e.g. analysis of mitochondrial dysfunction and proteins involved in the disease, survival of dopaminergic neurons, dopaminergic behaviors such as basal slowing of eating behavior or chemotaxis). These measurements will be performed on a range of low to high energy deposition, in order to compare the effects of low and high doses.
This work should result in at least two publications in peer-reviewed journals.
- Degree: Ph. D. in Biology, Bioengineering or Biomechanics.
- Skills required: The candidate will have strong skills in the field of microfluidics. General knowledge in biology, molecular biology, neurology will be appreciated.
- Required qualities: autonomy and rigour, analytical and synthesis skills, ability to work on multidisciplinary subjects, creativity, writing and oral presentation skills, team spirit.