Published online on March 26, 2019

Post-doctoral position
Measuring cellular compartmentation of brain lactate and its alterations during brain activity, plasticity and Alzheimer’s disease

Environment and context: MIRCen is a preclinical research center located in the French Atomic Energy Commission (CEA) center of Fontenay-aux-Roses (5 km south from Paris). MIRCen hosts the Unité Mixte de Recherche UMR 9199 (“Neurodegenerative Diseases Laboratory”), as well as several platforms dedicated to the development of animal models of neurodegenerative disease and to the evaluation of novel therapies. It gathers complementary expertise and methodologies, such as biochemistry, cell culture, gene transfer, confocal microscopy, PET imaging and MRI. In particular, MIRCen hosts an in vivo magnetic resonance spectroscopy (MRS) group. MRS allows the non-invasive quantification of intracellular metabolites in large brain regions and, through advanced diffusion-weighting techniques developed in MIRCen, can potentially be sensitive to the compartmentation of brain lactate. Lactate compartmentation, i.e. its distribution between neurons, glial cells and the extracellular space, is tightly linked to lactate metabolism, and in particular to the astrocyte-to-neuron lactate shuttle mechanism.

Job description: The present offer is for a 4.5-year post-doctoral position funded by a grant from the European Research Council (LactaDiff project, PI: Julien Valette) and available now. The overarching aims of the project are i) to develop diffusion-weighted MRS methods to determine brain lactate compartmentation non-invasively; ii) to compare these methods with invasive reference techniques in rodents; and iii) to transpose these methods in humans.
The post-doc will mainly work on the second aim, more specifically on the implementation and use of invasive reference techniques to determine brain lactate compartmentation in rodents (including during whisker stimulation and in Alzheimer’s disease models, where lactate compartmentation is expected to change). These reference techniques will consist in:

  • Implanted enzyme-electrodes for extracellular lactate concentration recording.
  • In vivo imaging of laconic FRET sensors for lactate quantification in neurons and glial cells. This will be achieved using a MR-compatible optical system dubbed SPEED (Single Photon Excitation and Emission Detection), developed by Bruno Weber’s team (Zurich University), and that we will duplicate in MIRCen with his help.

Throughout the project, the post-doc will work in close collaboration with other members of the project team, including experts in MRS acquisition and in diffusion modeling, as well as with the senior neurobiologists of the lab.

Candidate profile: The candidate should hold a Ph.D. related to neurobiology, neurochemistry, brain metabolism or similar fields. Salary will be commensurate with experience (past post-docs, etc…). He/she should be highly motivated, and willing to collaborate with people having different backgrounds, in particular physicists. The candidate should be fluent in English or in French. Experience in confocal microscopy, patch clamping, enzyme-electrode recordings or FRET imaging will be highly appreciated.

Contact info: CVs and application letters, as well as requests for additional information, should be sent to Julien Valette by email at the following address: julien.valette _at_ cea.fr