PhD candidate M/W Large-volume brain imaging using serial multicolor multiphoton microscopy


2 Sep 2023
Job Information

Laboratoire d’optique et biosciences
Research Field
Researcher Profile
First Stage Researcher (R1)
Application Deadline
22 Sep 2023 – 23:59 (UTC)
Type of Contract
Job Status
Hours Per Week
Offer Starting Date
1 Nov 2023
Is the job funded through the EU Research Framework Programme?
H2020 / ERC
Is the Job related to staff position within a Research Infrastructure?

Offer Description

The project will be carried out within the Optics and Biosciences Laboratory of the Ecole Polytechnique (Palaiseau) in the advanced microscopies team. The host team offers an interdisciplinary environment combining optics, computer science and biology. The work will involve daily interactions with a group of ~3-4 people, within a microscopy team of ~25 people, and interactions with collaborators in the ERC-SyG HOPE project (Institut de la Vision, Paris; INMED, Marseille). Ecole Polytechnique is located in the Paris-Saclay region, and is easily accessible by transport from Paris. Further information is available at . The candidate will join the doctoral school of the Institut Polytechnique de Paris, in the field of physics.

In vertebrates, the anatomy and structure of the brain are established during early development, and any abnormality during these crucial stages can lead to serious pathologies. However, the mechanisms that shape brain regions remain poorly understood, due to the technical difficulties involved in mapping opaque tissues with sub-cellular precision. To address these issues, the Laboratoire d’Optique et de Biosciences (LOB, Ecole Polytechnique, Palaiseau), in collaboration with the Institut de la Vision (IdV, Paris), has developed an original platform for 3D microscopy of large volumes of ex vivo mouse tissue, called serial color multiphoton microscopy (ChroMS). This method is based on two-photon multicolor frequency-mixing microscopy developed at LOB (Mahou, Nat Methods 2012), serial block imaging, and the ‘brainbow’ approach developed at IdV, which enables color labeling of neurons in a mouse brain (Livet, Nature 2007). A first demonstration of the performance of the ChroMS approach was published in 2019 (Abdeladim, Nat Comm 2019) and a second generation has recently been validated (H.Blanc, PhD thesis, expected defense 10/2023).
Building on this previous work, the thesis project will explore several complementary directions.
A first objective of the project will be to develop ChroMS for large-scale mapping of label-free nonlinear signals, such as second or third harmonic generation (SHG, THG) in model organs and organoids. Systematic mapping of THG signals will be useful for quantifying myelin distribution at different scales in the mouse brain. Mapping SHG signals at organ scale could be used to map muscle fiber distribution in heart models. Exploring this new application of the ChroMS platform will provide an opportunity to master its operation, from sample assembly to data reconstruction.
A second objective will be to explore adaptive optics approaches to minimize the progressive degradation in depth of resolution and signal-to-noise ratio. Deep tissue imaging is difficult due to aberrations caused by refractive index heterogeneity. This effect complicates image quantification. One strategy will be to homogenize the refractive index of the tissue using an index-matching medium, and characterize the advantages of this approach for 3D imaging. A complementary approach will be to explore the possibility of decorrelating spherical aberration using an active optical element.
A third objective will be to use the multicolor imaging capability of ChroMS to obtain reference datasets of color-coded cell lineages or connectivity in brains at different stages of development, in order to study clonal organization and circuit topography in different regions (cortex, hippocampus, cerebellum, spinal cord). The next step will be to establish automated image analysis strategies to extract quantitative data on cell and tissue morphology, as part of a collaborative project funded by the European Research Council (ERC).
Although based in physics, the project is interdisciplinary: the overall aim is to apply the imaging methods developed to analyze tissue organization and development in normal and pathological contexts. The work will involve interaction with researchers with complementary backgrounds in (i) nonlinear optics and microscopy, (ii) applied mathematics and computer science, (iii) genetic engineering and developmental neurobiology.


Research Field
Education Level
PhD or equivalent


Research Field
Years of Research Experience

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Laboratoire d’optique et biosciences

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