Multicellular dynamics and evolution in dense populations

密集群体中的多细胞动力学和进化

• 批准号: 455449456
• 负责人: Dr. Jona Kayser
• 金额: --
• 依托单位: Abteilung Biologische Optomechanik
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/455449456?language=en
• 关键词: Multicellular; dynamics; evolution; dense; populations

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.

细胞进化是生命最基本的概念之一，也是现代医疗保健中一些最紧迫挑战的根本原因，例如肿瘤发生和耐药性的进化。然而，迄今为止，大多数相关的进化实验都是在稀释的微生物种群或二维菌落中进行的。这意味着我们对三维实体肿瘤中组成细胞之间的不可分割的机械相互作用如何形成关键的进化驱动力知之甚少，如自然选择和遗传漂变。为了解决这些挑战，我提出了一种多学科的方法，将物理学的联合收割机概念，人口遗传学和癌症生物学与创新的遗传工具和复杂的细胞模型系统，以彻底改变我们如何研究进化，密集的细胞群使用一系列互补的微生物和癌细胞测定，我将研究（i）集体多细胞动力学如何影响遗传多样性和耐药性进化，（ii）3D中的集体细胞运动如何影响进化和治疗反应，以及（iii）细胞的机械特性及其对外力的敏感性如何重塑癌症类肿瘤中的自然选择和遗传漂变。将建立一个新的框架，将细胞进化描述为活性颗粒物质中的一种涌现现象，为实验进化领域的未来科学目标打开了大门。最后，所获得的见解的生物医学应用对于更好地理解肿瘤进展和耐药性演变至关重要，同时为改进癌症治疗的创新性基于进化的治疗策略提供跳板。