Postdoctoral researcher (M/F) for the development of a nonlinear fluorescence microscope with adaptive optics for monitoring intraneuronal transport at the molecular motor scale in vivo

Job Description

Missions

Molecular motors are key elements in the transport of molecules within cells, particularly in the long branches of neurons. This transport is disrupted at very early stages of neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. LuMIn (ENS Paris-Saclay) has already demonstrated the possibility of studying several parameters (speed, frequency of stops, etc.) in neuron cultures using the fluorescence of NV centers in diamond nanocrystals (NCs). These are internalized into cells by endocytosis, and the vesicle containing them is then taken over by molecular motors. The NC then serves as a light probe for their movement.

To give an order of magnitude, a molecular motor typically takes a step of 10 nm in about 10 ms. The spatiotemporal precision of these measurements has been recently greatly increased by developing a new two-photon microscope (the signal is no longer fluorescence but comes from second harmonic generation by the NCs). This microscope, using a fast digital holography device, allows BaTiO3 NCs (diameter ~130 nm) to be located in super-localization mode with spatial accuracy of approximately 5 nm and temporal accuracy of 2 to 5 ms in cell cultures on coverslips.

The aim of this project is to achieve the same performance in depth in biological tissues for the study of intraneuronal transport in vivo in animal models such as zebrafish, in collaboration with INRAE. This will be possible thanks to infrared illumination, which provides access to a window of transparency in biological tissues and depths of several hundred micrometers. However, tissues with a non-homogeneous optical index induce aberrations that alter the profile of the illumination beam during the tracking of a single NC and consequently degrade its localization accuracy. In order to maintain the accuracy of NC trajectory measurement, which is fundamental at the scale of a single molecular motor's dynamics, it is therefore necessary to correct aberrations over time to restore a diffraction-limited illumination beam. This will be achieved using an adaptive optics (AO) loop specially designed for in vivo two-photon microscopy, whose performance has already been demonstrated at ISMO.

Activity

The candidate will contribute to various aspects of the project:
- optical and optomechanical design, assembly and alignment, assembly control and synchronization of components
- characterization of the setup performances
- preparation of test and biological samples, data acquisition, data analysis
- communication (with project partners, conferences, publications)

Your Profil

Skills

- Knowledge and skills in physics/optics, particularly in instrumental optics and physical optics
- Knowledge in fluorescence microscopy and imaging of biological samples
- Skills in optical alignment
- Skills in control systems and Python programming
- Skills in data processing and image analysis
- Oral and written communication skills, ability to facilitate collaboration at the interface between physics, mathematics, and biology

Your Work Environment

This multidisciplinary work will be carried out at ISMO within the interdisciplinary NanoBio team (CNRS/Paris-Saclay University Joint Unit) in close collaboration with LuMIn at ENS Paris Saclay, as part of an ANR contract, with a consortium of six partners.

Compensation and benefits

Compensation

Gross monthly salary depending on experience: from 3131,32 € to 4341,70 €

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions