Project description
How Dendritic Cells migrate with large cargo
Dendritic cells (DCs) are immune sentinels, which ingest material and transport it to the draining lymph nodes to drive adaptive immunity. In environments containing mixed material, DCs need to migrate or move through a number of physical obstacles. Initial findings suggest that DCs deform or rotate very large particles and, at times, exhibit nuclear deformation or some form of migratory limitation, resembling observations made in vivo. The DCsConCargo project will make use of tunable oil droplets, paramagnetic beads, and 3D-printed microplastic particles, and in vitro models (collagen gels and PDMS microchannels) to study the ability of mouse bone marrow-derived DCs to transmigrate through constricted spaces while carrying large cargo. The aim is to understand how DCs are able to navigate complex tissue environments.
Objective
As immune sentinels, dendritic cells (DCs) must be able to ingest material and migrate to lymph nodes to present the processed antigen to T cells, and initiate the adaptive immune response, essential against pathogens or cancer. This means that DCs must be able to navigate through complex environments with this ingested material of varying physical characteristics. Preliminary data revealed that DCs deform and/or rotate large, ingested material to overcome occlusion from entering constriction points (transmigration). Additionally, there are instances of nuclear deformation and even migratory frustration, which reflect reported phenomena of DCs in vivo in mice. I propose to use a suite of fabricated particles and in vitro complex environments to test the ability of mouse bone marrow-derived dendritic cells to overcome physical obstacles with large cargos. The fabricated particles will include oil droplets with tunable deformability, paramagnetic particles, and 3D printed microplastics. The in vitro complex environments are collagen gels and PDMS microchannels where I can observe DCs with ingest particles attempting to through points of constriction. With this experimental set-up, I can measure the efficiency of transmigration, deformation or rotation of particles, as well as the force exerted on particles as a function of particle properties. Furthermore, I can observe the effect of particle manipulation on DC behavior and function, even if they never successfully transmigrate. This work will aim to answer how dendritic cells can migrate successfully with a wide range of materials, but also provide insight into the role of frustrated or trapped DCs that are observed in tissues, and particularly near tumors.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
- natural sciences earth and related environmental sciences environmental sciences pollution
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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75231 Paris
France
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