OSS · Spatio-temporal control of the Src kinase activation through Optogenetics in Cell invasion
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-03-01 → 2018-02-28
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Spatio-temporal control of the Src kinase activation through Optogenetics in Cell invasion
The OSS project investigated how the same oncogene (a gene that causes cancer) named Src can control different cellular signalling circuitries and consequently different cell behaviors. Our hypothesis is that Src signalling should be regulated in space and time to be able to induce many behaviors, including cell invasion, important for cancer cell dissemination. Cell invasion is based on adhesive structures named invadosomes that are responsible for microenvironment degradation which is crucial for cancer metastasis. Src controls both assembly and disassembly of invadosomes. It is puzzling to understand how one single protein can affect opposite functions of the same structure. The OSS project is based on the development of a very innovative technique named optogenetics, which allows to turn on and off the molecule Src, by simply enlightening the cell with blue light. Being able to control Src activity in space and time might help for fighting cancer cell dissemination. Furthermore, it would represent a major advance in Src oncogene targeted therapy.
Data: CORDIS, © European Union
Project objective
Cell signaling is a complex system that coordinates cell actions in response to environmental inputs. Signaling pathways are often seen and investigated as on/off networks, but the reality of the intensities and spatio-temporal organization of these networks has been poorly integrated with the dynamics of cellular outputs in response to specific environmental inputs. In the OSS project we aim to approach this general problem by focusing on a specific cellular function, cell invasion (the hosts area of expertise). We propose to 1) use the formation of invadosomes, characteristic acto-adhesive structures important for cell invasion as a specific cellular function, to address these fundamental questions 2) and target the pleiotropic tyrosine kinase Src that has the ability to induce cell invasion globally by acting on cell adhesion, migration, contractility and invadosome dynamics independently of any environmental regulation, to investigate how a biological signal can be dynamically encoded into specific multifarious cellular outputs. Our hypothesis is that specific spatio-temporal patterns of Src activation could be the basis of its pleiotropicity. Thus, the first step of the OSS project will be to use Src biosensors to observe different patterns of Src activation and correlate them with the dynamics of Src-dependent cellular outputs (such as induction of invadosomes). Secondly, we will directly control spatio-temporal Src activity in live cells using optogenetics, a powerful and innovative approach that will allow us to mimic the observed patterns of Src activation and to create new patterns in order to explore dynamic equilibrium between Src signaling and its specific cellular outputs. This project is at the cross-road of signaling theory in biology, cell biology of acto-adhesive structures and biotechnology fields. The goal of the OSS project is to actively manipulate signals in space and time with the ultimate aim to control dynamic process of cell invasion.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union