DynaSpaCER · Molecular Mechanisms of Dynamic and Spatial Control of Eph Receptors clustering
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-03-01 → 2018-02-28
- EU contribution
- €185,857
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Molecular Mechanisms of Dynamic and Spatial Control of Eph Receptors clustering
The aim of DynaSpaCER was to understand how cell communicate when touching each other. Cellular surface is covered in proteins called receptors that upon contact recognize their matching pair (ligand), start reorganizing forming aggregates and undergo to a chemical modification that leads to signal transduction from one cell to the other. All these events happen to a length and time scale that is not easily accessible and currently there is not a unique technology that on its own could give a clear picture of how the proteins on the surface are reorganized during the interaction of two cells. In order to overcome this challenge during the project we develop a combined approach mixing advanced techniques ranging from DNA nanotechnology to high-resolution microscopies via standard biochemical techniques and computational tools to get an insight of what are the molecular interactions involved at the cellular membrane and what kind of signals are triggered. As a model biological system, we investigated a particular kind of protein (Eph receptors) that has been show to be present in high quantity on the outer membrane of some type of cancer cells. The project explored new ways to target receptor signaling at the nanoscale and has established a basis to open new avenues of investigation of fundamental mechanisms in membrane biology and of knowledge-based drug development.
Data: CORDIS, © European Union
Project objective
There is mounting evidence that the spatial and temporal organization of ligands at cell-cell interfaces modulates signaling. In particular, for Eph receptors and their ligands (ephrins) this phenomenon is widely recognized but poorly understood due to difficulties in controlling and analyzing membrane protein microenvironments at the nanoscale. A combination of different techniques ranging from DNA nanotechnology to high resolution microscopies via standard biochemical techniques and computational tools will be used to provide a molecular understanding of the roles of the spatial and temporal organization of ligands in receptor signaling. Substrates that recreate the intramembrane signalling geometry at cell-cell contacts are designed and produced by employing ligand decorated DNA nanostructures anchored on artificial supported lipid bilayers. This allows an unparalleled control of spatial distribution of the ligands and their dynamics. TIRF/STORM super-resolution microscopy is used to measure size and dynamics of clustering and biochemical assays will quantify the receptor spatial distribution and activation levels. Together with computational simulation and modeling of clustering dynamics, these efforts will lead to a molecular mechanism of spatial organization of ligands and receptors during clustering and how this affects signaling.
Original text from CORDIS.
Participants
- KAROLINSKA INSTITUTET · STOCKHOLMCoordinatorSweden
Links
Data: CORDIS, © European Union