Sujet: Development of a dedicated microsystem for the selective capture of uranium-target proteins in a cell line
Lieu : UMR CNRS 8612- Institut Galien Paris Sud, Equipe : protein and nanotechnology in analytical science (PNAS) en collaboration avec 2 équipes du CEA Saclay
Faculté de Pharmacie, 92290 Châtenay Malabry
Direction : Dr Thuy tran (phone: 01.46.83.59.03) and Carole Bresson (phone: 01.69.08.83.48)
Date: à partir de janvier 2018
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 (UO22+) onto the monolith. The selective capture of reference UO22+-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 UO22+-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. .
To apply, send an email with detailed CV, list of publications, and motivation letter to :
Dr Thuy tran (phone: 01.46.83.59.03) PNAS, Institut Galien Paris Sud, Université Paris Sud, Châtenay Malabry
Carole Bresson (phone: 01.69.08.83.48) DPC/SEARS/LANIE, CEA Saclay
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. The candidate will be in charge of the project management, covering performing experiments, analysis and reporting of results. She/he is expected to be highly autonomous and innovative, to demonstrate ability to write, communicate and work in an interdisciplinary approach. Experiments will be carried out in the laboratories of each of the partners, so the candidate must be able to adapt and integrate quickly different environments.
Deadline: application before november 2017