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Vacancy:   CEA-Saclay (Paris, France): Development of a dedicated microsystem for the selective capture of uranium-target proteins in a cell line

*Duration:* 2 years.
*Starting date:* Beginning of 2018.
*Financing:* French Alternative Energies and Atomic Energy Commision (CEA, *Commissariat à l'énergie atomique et aux énergies alternatives*).

The miniaturization of analytical steps commonly carried out in the laboratory allows for fast and sensitive analysis of very small amount of compounds in complex matrices. Experimental replicates of micro-sized samples, like some biological samples, can also be performed. Furthermore, downscaling entails a reduction of the solvent and reagent consumption, waste production and analysis time.

The aim of this project is the development of a microsystem dedicated to the capture of proteins able to selectively bind U in a human neuronal cellular model, according to the IMAC mode (Immobilized Metal Affinity Chromatography), for further identification of such target proteins. The knowledge of these intracellular proteins will provide invaluable clue to decipher the uranium neurotoxicity, hardly known, but is still a great challenge due to the microscale of the samples and the trace levels of such biomolecules. The strategy is based on the integration of a monolith in the channel of a microsystem, in combination with the functionalizing ability of this support for immobilization of different metal ions onto its surface. The in situ synthesis and further anchorage of a phosphate monolith will be set up in the microchannel of a chip, in order to immobilize uranium as uranyl form (UO2 2+) onto the monolith. The selective capture of reference UO2 2+- binding proteins and their quantification by targeted mass spectrometry, will allow to demonstrate the proof of concept of this microsystem as well as the benefits provided by miniaturization.

This dedicated microsystem will be further applied to the selective capture of unknown UO2 2+-binding proteins in a human neuronal cellular model before their identification by a proteomic approach. The information obtained from this step will be the starting point to make hypothesis regarding to the nature and the role of these proteins, in connection with the neurotoxicity mechanisms of uranium.

Job description: This post-doctoral project will be led in collaboration between three laboratories:

- LANIE (Laboratoire de développement Analytique Nucléaire, Isotopique et Elémentaire), Service d'Etudes Analytiques et de Réactivité des Surfaces, CEA Saclay (Host laboratory)

- PNAS (Proteins and Nanotechnology in Analytical Science), Institut Galien Paris Sud, Châtenay Malabry

- LEMM (Laboratoire d'Etudes du Métabolisme des Médicaments), Service de Pharmacologie et Immunoanalyse, CEA Saclay.

The candidate will benefit from the skills and the instrumental means of each of the partners in the field of analytical technique miniaturization, coupling chromatographic and electrophoretic separation techniques with different mass spectrometers (ESI MS and ICP MS), high precision elemental and isotope analyses and proteomic analysis.

Qualification: PhD in the field of analytical chemistry, with a strong background in microsystem development and if possible in *in situ* photochemical synthesis of monoliths. Skills in biochemistry will be valuable.

To apply, send an email with detailed CV, list of publications, and motivation letter to:
carole.bresson@cea.fr, DPC/SEARS/LANIE, CEA Saclay - Phone: thuy.tran-maignan@u-psud.fr, PNAS, Institut Galien Paris Sud, Université Paris Sud, Châtenay Malabry - phone : 01 46 83 59 03

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