FNS-4-NAMOSAT · Development of fluorescence nanospectroscopy to elucidate the roles of nanoscale molecular segregation in the activation of T-cells
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-10-01 → 2018-09-30
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Development of fluorescence nanospectroscopy to elucidate the roles of nanoscale molecular segregation in the activation of T-cells
Understanding of molecular mechanisms of cellular processes is required in order to efficiently prevent, diagnose, and treat diseases. However, many of such key molecular events, including the first steps of the activation of the immune response, remain elusive due to the lack of experimental methodologies that could track these fast events on the molecular level in living cells. Nowadays, super-resolution fluorescence microscopy techniques allow us to non-invasively locate molecular structures of interest with a great precision, whereas spectroscopic methods provide rich information about molecular properties of the studied environment. 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.
Data: CORDIS, © European Union
Project objective
BACKGROUNDNanoscale protein and lipid heterogeneities, e.g. lipid rafts, have been detected in numerous membrane-related cellular processes, including the initiation of the immune response upon T-cell activation. However, the interplay of protein and lipid segregation remains unclear.PROBLEMSuper-resolution fluorescence microscopy can localize such supramolecular structures, but reveals little information on their identity. In contrast, (micro)spectroscopies with environment-sensitive probes can identify local molecular properties, but lack the appropriate spatial resolution for their localization.AIMThe main research goal of the Action is to establish an original method with suitable resolution and sensitivity to improve our understanding of lipid reorganization during the activation of T-cells.SOLUTIONWe will develop fluorescence nanospectroscopy (FNS) by combining STED microscopy, spectral detection, and environment-sensitive probes, to achieve the sensitivity to local molecular properties with nanoscale spatial resolution.IMPACTBesides new insights into molecular mechanisms of immunity, FNS will importantly complement the available methods by probing local molecular order, facilitating FRET measurements, super-resolved spectral imaging etc. It will enable further advances in numerous fields of molecular and cell biology where membrane proteins and lipids act in a precisely coordinated manner.TRAININGThe Researcher will be enrolled in the world-leading environment in the fields of STED microscopy, membrane structure and dynamics, and immunology. The acquired deep knowledge on the subjects of research, gained solid experimental and leadership skills from the Supervisor, invaluable experience from a cross-sectoral visit in the collaborating company, as well as his integration into the network within the scientific communities of planned multidisciplinary research activities, will decisively boost his future career as an independent life scientist.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union