Biosensor Design · Engineering Chemotactic Biosensors for a Diverse Spectrum of Metastatic Markers
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-02-01 → 2022-01-31
- EU contribution
- €191,149
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Engineering Chemotactic Biosensors for a Diverse Spectrum of Metastatic Markers
The directional movement of cells in response to environmental signals (chemotaxis) is essential in biology. Immune cells use chemotaxis to traffic towards disease sites, however, metastatic cells often remain undetected. The design of chemotactic biosensors for metastatic markers can manipulate the immune system's spectrum of actions. Studies have identified soluble secreted factors that promote the initial escape of tumour cells, their intravasation into circulation, and extravasation into metastatic niches. The EU-funded Biosensor Design project aims to build and validate a general computation-based platform for rational biosensor design. The immediate objective is to create biosensors that will elicit migration of engineered cytotoxic immune cells towards vulnerable metastatic cells.
Data: CORDIS, © European Union
Project objective
Directional movement of cells in response to environmental cues (e.g. chemotaxis) is essential throughout biology, and the membrane receptors that initiate cell migration offer a key opportunity for modulation by synthetic biologists. The design of chemotactic receptor biosensors for metastatic markers has the potential to expand the immune system’s spectrum of actions. Metastatic cancers are extremely lethal, and tumor cells that escape to seed a secondary tumor in a distant organ often escape immunosurveillance. Extensive studies on metastasis have identified soluble secreted factors that promote the initial escape of tumor cells, their intravasation into circulation, and extravasation into metastatic niches where they can proliferate and form new malignant tumors. We will employ a host of computational design techniques developed in the Barth Lab to build novel biosensors that will elicit chemotactic responses towards molecular indicators of metastatic cells at various key points during their journey to secondary sites when they are vulnerable to engineered cytotoxic immune (T and NK) cells. By harnessing the migratory potency of a chemokine receptor scaffold, we will design several novel chemotactic receptors sensing molecules of increasing complexity to ultimately build and validate a general computation-based platform for rational biosensor design. At a fundamental level, engineering membrane receptors that can respond to a diversity of molecules is a stringent test of our biophysical understanding of protein structure and function, but also has far-reaching applications in basic and translational research with immediate relevance and impact for cancer therapeutics.
Original text from CORDIS.
Participants
- ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneCoordinatorSwitzerland
Links
Data: CORDIS, © European Union