"We aim to design smart substrates and suitable detection techniques to understand better the dynamics and spatial organization found in the immunological synapse, with the ultimate goal of developing new diagnostic tools for sensitive detection of immune deficiency diseases that arise from faulty adhesion. The immunological synapse (IS), formed at the interface between a T-lymphocyte and an antigen presenting cell, has been the target of intense multidisciplinary research in the last decade. Studies point to a crucial role for adhesion mediated by protein clusters for the stability and activity of the synapse. However, even the cluster size - micro or nano scale - remains contentious. Furthermore, while in vivo, the synapse is formed in a soft 3D environment, most in vitro experiments are on hard 2D surfaces. Clearly, one way to probe how the micro/nano environment of the T-cell influences the IS is by interrogating it with artificial substrates that are soft, three dimensionally structured and exhibit motifs down to the cluster length-scale. We shall develop 3D and soft polymeric structures with controlled placement of adhesion molecules and antigens on a single molecule level. The structure, assembly and signalling for stable as well as dynamic IS, on such substrates, will be investigated. Mechano-transduction at IS will be probed by using soft substrates of tunable Youngs modulus. Advanced optical techniques will be developed for quantitative and dynamic mapping of proteins and the cell-cell interface topography. Quantitative reflection interference contrast microscopy, will permit characterization of adhesion of native cells without the need of a special labelling strategy. Our advanced substrates and observation techniques will open up new ways to probe inter-cellular adhesion in general and the immunological synapse in particular. The acquired knowledge will be used for fabricating a cell sensor device for diagnosing T-cell pathology."
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