deCiphering tHE chemo-mechanical CrosstalK between Macrophages And Tumor cElls

Description du projet

Diaphonie entre macrophages et cellules cancéreuses

Les macrophages sont des cellules immunitaires clés responsables de la digestion des substances étrangères, des agents pathogènes et des cellules cancéreuses. Comprendre comment ces cellules migrent au sein des tumeurs en réponse à des signaux extracellulaires est primordial pour exploiter leur pouvoir immunothérapeutique. Pour ce faire, le projet CHECKMATE financé par l’UE étudiera l’influence des signaux chimiques et mécaniques sur la migration des macrophages. Les scientifiques utiliseront des échafaudages 3D et des agrégats de tumeurs pour surveiller la migration des macrophages après stimulation avec différents facteurs de croissance et chimiokines. Ils appliqueront également une contrainte mécanique et tenteront de récapituler des conditions variables d’oxygène et de glucose. Les résultats permettront de brosser un tableau plus détaillé de l’activation, de la migration et de la fonction des macrophages dans le cancer.

Objectif

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.

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