CHECKMATE · deCiphering tHE chemo-mechanical CrosstalK between Macrophages And Tumor cElls
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-03-15 → 2023-03-14
- EU contribution
- €196,708
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
deCiphering tHE chemo-mechanical CrosstalK between Macrophages And Tumor cElls
The CHECKMATE project focused on the influence of biophysical stimuli on the immune response of macrophages. Macrophages are cells of the immune system that constantly patrol the body in search of foreign objects that could harm the organism. They are also involved in the regulation of other immune cells and are extremely important for the removal of waste (dead cells, cell debris, etc.) from healthy tissues. Macrophages are well known to respond to a variety of biochemical inputs, in the form of cytokines or growth factors secerned from other cells. In addition, it is becoming increasingly clear that macrophages have as well mechanosensitive capabilities, i.e., they can sense alterations in their mechanical environment. These cells have been shown to behave differently depending on the rigidity of the substrate on which they are placed; it has also been shown that macrophages respond differently when subject to static or dynamic mechanical solicitations. However, deciphering how this mechanical sensitivity modulates the response of macrophages to biochemical inputs is still widely unclear. In this research project we aimed to address this fundamental question, making use of both experimental and theoretical tools from biophysics. A better understanding of such mechanisms is vital for the development of novel immunotherapies, which could improve the quality and expectancy of life for several categories of patients.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- UNIVERSITE GRENOBLE ALPES · GrenobleCoordinatorFrance
Links
Data: CORDIS, © European Union