Multicellular dynamics and evolution in dense populations

点击翻译按钮获取中文摘要

Cellular evolution, while being one of the most fundamental concepts of life, is also the root cause for some of the most pressing challenges in modern health care, such as oncogenesis and the evolution of drug resistance.Yet, most pertinent evolution experiments to date have been conducted in dilute microbial populations or 2-dimensional colonies. This means we know little about how the immanent mechanical interactions between the constituent cells in 3-dimensional solid tumors shape key evolutionary driving forces, such as natural selection and genetic drift.To address these challenges, I propose a multidisciplinary approach that will combine concepts from physics, population genetics and cancer biology with innovative genetic tools and sophisticated cellular model systems to revolutionize how we study evolution in dense cellular populations. Using a series of complementary microbial and cancer cell assays, I will investigate (i) how collective multicellular dynamics impact genetic diversity and drug resistance evolution, (ii) how collective cell motion in 3D affect evolution and treatment response, and (iii) how the mechanical properties of cells and their susceptibility to external forces reshape natural selection and genetic drift in cancer tumoroids.The completion of this proposal will establish a new framework describing cellular evolution as an emergent phenomenon in active granular matter, opening the door to future scientific objectives in the field of experimental evolution. Finally, biomedical application of the insights gained will be essential to better understanding tumor progression and drug resistance evolution while providing a springboard for innovative evolution-based treatment strategies for improved cancer therapy.