Periodic Reporting for period 1 - FNS-4-NAMOSAT (Development of fluorescence nanospectroscopy to elucidate the roles of nanoscale molecular segregation in the activation of T-cells)
Reporting period: 2016-10-01 to 2018-09-30
The main aim of this project was therefore to couple the strengths of super-resolution STED microscopy and of fluorescence spectroscopy employing environment-sensitive probes, into fluorescence nanospectroscopy (FNS), to offer new insights into the molecular arrangements, such as nanoscale lipid heterogeneities, in the membranes of T-cells upon their activation. We found out that the key membrane protein, the T-cell receptor (TCR), changes its preference for its membrane environment once engaged in signalling clusters, which importantly complements our understanding of the functional interplay between proteins and lipids in the membranes of living cells.
The specific findings about membrane organisation in activating T-cells (Santos et al., Nat. Immunology, 2018), contribute to clarifying the long-standing mystery of the roles of lipid heterogeneities in the initiation of the adaptive immune response. This might therefore elucidate the origins of the immune disorders (e.g. autoimmune diseases, allergies, and immune evasion of cancer) and hence help towards the design of new therapies, bringing long-term benefits to the society.