A post-doctoral position is available to develop a 3D model of a human lymph node and apply this model to preclinical vaccine evaluation. The successful applicant will join the team of Lisa Chakrabarti at the Pasteur Institute in Paris. The position is fully funded for 3 years in the frame of an industrial contract.
Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-on-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D matrix. Perfusion of the SARS-CoV-2 Spike mimicked a vaccine boost, by inducing a massive amplification of memory B cells and Spike-specific antibody secretion. (R. Jeger-Madiot et al., J Exp Med 2024). Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters, were recapitulated in the LO chip. Further, cells within the chip were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines in the LO chip.
The project will aim at further developing the LO chip platform, to better mimic lymphoid tissue organization and function. The candidate will test new chip designs to promote the formation of a T cell zone and a B cell zone, with the aim of achieving de novo antigenic priming. The candidate will also aim at inducing conditions for mucosal imprinting on the LO chip, to better evaluate the potential of candidate mRNA vaccines to target mucosal pathogens. Further developments will aim at evaluating the predictive power of the LO chip assay and at increasing its throughput, with the objective of building a novel pipeline suitable for the preclinical evaluation of candidate vaccines. The project will be carried out in close collaboration with the team of Samy Gobaa at the Microfluidics and Biomaterials core facility of the Pasteur Institute.
Recent publications:
– Robinot R., Hubert M., …, Schwartz O.*, and Chakrabarti L.A.* (2021) SARS-CoV-2 infection damages airway motile cilia and impairs mucociliary clearance. Nature Communications 12: 4354.
– Claireaux M., Robinot R., …, Lambotte O., and Chakrabarti L.A.* (2022) Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry. Nature Communications 13:521
– Jeger-Madiot R*, Planas D, Staropoli I, …, Gobaa S, and Chakrabarti LA*. (2024) Modeling memory B cell responses in a Lymphoid Organ-Chip to evaluate mRNA vaccine boosting. Journal of Experimental Medicine 221(10):e20240289.
Qualifications:
We are looking for a skilled and highly motivated candidate with:
- a PhD in immunology, with expertise in T cell/B cell interactions and/or vaccinology
- an expertise in advanced cytometry
- a strong motivation to learn organ-on-chip technologies
- a track record of publications in relevant scientific fields
Expertise in tissue engineering will be an asset. Good communication skills in spoken and written English are essential.
Application:
Interested candidates should submit their application with a detailed CV, a cover letter detailing skills and motivation, and contact information for 2/3 references to Lisa Chakrabarti: chakra (at) pasteur (dot) fr
Web site: https://research.pasteur.fr/en/team/group-lisa-chakrabarti/