Description du sujet de thèse

T lymphocytes identify foreign antigens through physical interactions with target cells, forming an immunological synapse. The strength and spatial organization of molecular bonds within this interface determine immune response outcomes, such as whether a cytotoxic T cell should destroy or ignore a cancer cell. It is thus important to quantify the strength of the adhesion within the immunological synapse, depending on the composition and on the single-bond binding energy.

The aims of the projects are to:
- develop methods to measure adhesion forces between T cells and antibody-coated microbeads,
- extracting single-molecule binding energies from cell adhesion measurements,
- analyze how adhesive patches evolve over time,
- investigate how different ligand-receptor contributions (activating and co-activating molecules, adhesion molecules) combine in the immunological synapse.

We will address the following research questions:
- how do cellular viscoelastic properties influence adhesive interactions?
- can we reliably extract single-molecule binding energy from whole-cell measurements?
- how do adhesive patches evolve temporally, and are the important time scales related to the organization of the T cell at the interface ?
- how do different ligand-receptor bonds collectively function in T cell-target cell interactions?

During this interdisciplinary thesis with a major experimental component, we will use our micropipette-based single-cell rheometer to perform cell microindentation to (i) quantify viscoelastic properties of T cells, (ii) measure their adhesive properties to antibody-coated microbeads and various cell types. We will collaborate with immunologists (Claire Hivroz group, Institut Curie, Paris) and biologists for cell/molecular expertise and work with theoreticians to analyze mechanical measurements (David Gonzalez-Rodriguez, Univ. de Lorraine, Metz)

The candidate should have a background in experimental physics, bioengineering, or related fields, with experience in or willingness to learn cell culture techniques. The candidate should also have basic programming languages (e.g. Python, MATLAB, or ImageJ/Fiji) for data analysis and image processing, and strong communication skills for effective collaboration with scientists from diverse backgrounds including immunologists and theoreticians.

Contexte de travail

The Hydrodynamics Laboratory (LadHyX) is located on the Ecole Polytechnique campus in Palaiseau, near Paris, France. Julien Husson's research group specializes in experimental cell mechanics. The thesis research will be conducted at LadHyX in collaboration with immunologists from Claire Hivroz's group at Institut Curie in Paris, biologists providing cellular and molecular expertise, and theoreticians led by David Gonzalez-Rodriguez at the University of Lorraine in Metz for mechanical measurement analysis.