deCiphering tHE chemo-mechanical CrosstalK between Macrophages And Tumor cElls

Descripción del proyecto

Comunicación cruzada entre macrófagos y células cancerosas

Los macrófagos son células inmunitarias fundamentales responsables de digerir sustancias extrañas, patógenos y células cancerosas. Para poder aprovechar todo el potencial inmunoterápico de estas células, resulta esencial comprender cómo migran en el interior de los tumores en respuesta a señales extracelulares. Con tal fin, el proyecto financiado con fondos europeos CHECKMATE investigará la influencia de las señales químicas y mecánicas sobre la migración de los macrófagos. Los científicos aplicarán matrices tridimensionales y agregados tumorales para supervisar la migración de macrófagos tras una estimulación con diferentes quimiocinas y factores de crecimiento. Además, aplicarán estrés mecánico e intentarán recapitular condiciones variables de oxígeno y glucosa. Los resultados contribuirán a obtener una visión más completa de la activación, migración y función de los macrófagos en el cáncer.

Objetivo

Pietro Mascheroni received his training in applied mathematics and mechanics in Italy and has carried out his research in the United States and in Germany. His work lies at the interface between applied mathematics and biology and has been published in prominent journals of the field. He is requesting funding for two years to work with Giovanni Cappello and join his group at LIPhy Grenoble, France. The scientific aim of the project is to improve the understanding of macrophage response to external cues, with the final goal of drawing new insights into the mechanisms of action of immunotherapies. The action will investigate the influence of chemical and mechanical signals on macrophage migration, analyzing their respective importance in determining cell behavior. Taking advantage of the host laboratory’s expertise and facilities, dynamic light scattering will be employed to monitor macrophage migration in 3D scaffolds and tumor aggregates. Macrophages will be stimulated by using different growth factors and chemokines, under variable oxygen and glucose culturing conditions. Mechanical stress will be applied using microfluidic tools and exploiting the osmotic action of Dextran on the extracellular matrix. Relying on the applicant’s expertise, theoretical models based on the active gel theory will be developed to assist the understanding of experimental results. Throughout the project the medical implications of the research will be considered, by taking advantage of collaborations with clinicians of partner institutions. The training program of the action is exhaustive and will allow the researcher to grow as a world-class leader in this field, which is fundamental in healthcare for the benefit of society. He will develop a unique blend of knowledge and expertise, allowing him to communicate and work with applied mathematicians, biomedical scientists and clinicians in industry, health services and academia.

Ámbito científico (EuroSciVoc)

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