Coordination Funds

复杂真核生物的进化伴随着划分和分离细胞过程的需要，通常以被膜包裹的细胞器的形式存在，如细胞核、线粒体、内质网、高尔基体、内质体和溶酶体，它们具有教科书知识的地位。膜包裹与发展某种形式的运输系统，使生物分子可以在细胞器之间交换的问题有关。其他已知的隔室是无膜细胞器，如核仁、压力颗粒或卡哈尔小体。然而，直到最近十年才清楚的是，这些隔室是从相分离的物理过程中产生的，这赋予了它们非常特殊的性质；它们可以是可逆的、高度动态的，并且它们不需要特定的运输系统就能不断地与周围环境交换分子。这些特性要求我们重新思考细胞的组织，并发展我们现有的细胞运输和功能划分和调节的概念，为‘细胞生物学2.0’奠定基础。为了研究这些新出现的概念，并阐明通过相分离及其调控来实现细胞区隔的机制，我们还需要开发新的工具和方法，并将细胞生物学和生物物理学与生化重组以及理论和模型相结合。这一学科的结合将使我们能够对相分离在不同生物过程中的作用做出可测试的预测，这将在相关的功能生化分析以及细胞生物学、发育和疾病模型中得到验证。过去十年的相分离研究仅仅触及了生物分子凝析油复杂性的皮毛。最初对相分离作用的兴奋最近已经扩展到包括更多固体类型的凝析油，这使得能够进行额外的功能调节。这一国家优先计划汇集了来自不同领域、思维环境和科学背景的科学家。这个网络将使研究人员能够协同破译如何在缩合过程中产生新的功能以及病理，以及什么分子基础促进和调节这一关键过程。通过这样做，该计划将培养新一代科学家，他们挑战现有领域的边界，并通过凝析油的镜头解决生命科学中正在出现的重要问题。

The evolution of complex eukaryotes went along with the need to compartmentalize and separate cellular processes, often in the form of membrane-encapsulated organelles like the nucleus, mitochondria, the endoplasmic reticulum, the Golgi apparatus, endosomes and lysosomes, which have the status of textbook knowledge. Membrane encapsulation was associated with the problem of developing some form of transport system such that biomolecules can exchange between organelles. Other long-known compartments are membraneless organelles, such as nucleoli, stress granules or Cajal bodies. However, only within the last decade it has become clear that these compartments arise from the physical process of phase separation, which bestows them with very special properties; they can be reversible, highly dynamic, and they continuously exchange molecules with their surroundings without the requirement of specific transport systems. These properties require us to rethink the organization of cells and to evolve our existing concepts of compartmentalization and regulation of cellular transport and functions, setting the stage for ‘cell biology 2.0’. To investigate these newly emerging concepts and elucidate the mechanisms that underlie cellular compartmentalization via phase separation and regulation thereof, we also need to develop new tools and approaches and combine cell biology and biophysics with biochemical reconstitution as well as theory and modelling. This combination of disciplines will allow us to make testable predictions about the role of phase separation in diverse biological processes, which will be validated in relevant functional biochemical assays as well as cell biological, developmental and disease models. The last ten years of phase separation research have only scratched the surface of the complexity of biomolecular condensates. The initial excitement about the role of phase separation has recently been extended to include more solid types of condensates which enable additional layers of functional regulation. This national priority program brings together scientists from diverse fields, thinking environments and scientific backgrounds. This network will allow researchers to synergistically decipher how novel functions, but also pathologies, emerge from the process of condensation, and what molecular underpinnings facilitate and regulate this key process. By doing so, this program will nourish a new generation of scientists who challenge the boundaries of existing fields and tackle important emerging problems in the life sciences through the lens of condensates.