Deciphering multilevel cell to cell communication through microfluidic and plasmonic decoders

Descripción del proyecto

Descifrar la comunicación entre las células cancerosas

Una de las características de la metástasis es la interacción dinámica entre las células cancerosas y el microentorno tumoral. Sin embargo, la mayor parte de los estudios sobre comunicación intracelular se han centrado en señales aisladas, lo que dificulta el análisis conjunto de las complejas redes de comunicación implicadas y ofrece una visión parcial de la proliferación y la diseminación del cáncer. Para superar esta limitación, en el proyecto OBSERVER, financiado por el Consejo Europeo de Investigación, se desarrollará un dispositivo optofluídico en miniatura capaz de encapsular células individuales en diminutas gotas y seguir sus interacciones en tiempo real. La integración de microfluídica, nanosensores, transcriptómica e inteligencia artificial permitirá detectar señales químicas y comprender mejor los patrones de crecimiento y las respuestas moleculares. Los resultados contribuirán a ampliar el conocimiento sobre la comunicación entre células cancerosas y sentarán las bases para nuevas investigaciones en oncología de precisión.

Objetivo

As with the oversimplification of nuances in human communication, the focus in the analysis of communication between cells has been mainly atomistic. Considering only one communication type (e.g. verbal/non-verbal/visual/written) between two individuals hinders the understating of the scope and outcome of the interaction. Similarly, it is not possible to fully comprehend cell-to-cell communication by focusing exclusively on a specific communication level. Current monitoring methods of cell-to-cell communication do not allow simultaneous multilevel analyses. Exploring cell-to-cell communication at those individual levels limits the understanding of metastatic activation mechanisms as a complex and dynamic event. OBSERVER proposes a holistic bottom-up approach to decode cell-to-cell communication as a multilevel event through the development of an optofluidic decoder. For this, a microfluidic platform will be developed for the co-encapsulation and co-culture of two different cell types, while integrating an ultrasensitive anisotropic gold-based plasmonic selector and sensor. This platform will not only allow the real-time, high-throughput and dynamic monitoring of interactions during cell signalling and proliferation, but also transcriptomic downstream analyses. OBSERVER is radical as the consecution of this ambitious project will unlock new research agendas related primarily to the development of bleeding-edge tools supporting the understanding of cell-to-cell communication in cancer and metastasis. OBSERVER technology will provide the research community with thousands of heterogeneous single-cell paired models for drug testing, cell signalling or targeted discovery, thus accelerating cancer research. Further, the use of a novel set of devices will also boost microfluidics and plasmonics towards a new ground, while interfacing those with advanced data analytics and multimodal AI.