Coordination Funds

细胞松果糖是由真菌产生的天然产物，具有许多强大的生物活性。它们与肌动蛋白强烈结合，从而显著影响真核细胞。它们还在原核生物中表现出显著的生物活性，并在肌动蛋白不能成为靶点的情况下作为抗病毒化合物。它们抑制蛋白质合成、糖运输、植物生长、肿瘤坏死因子和血管生成，并参与真菌对植物和昆虫的免疫抑制和毒力和无毒，尽管这些过程的大多数分子机制尚不清楚。细胞松弛素是由氨基酸和聚酮组成的，它们通常是氧化定制的。已知的家族成员有数百个，但关于结构活性关系的系统研究报道很少，因为商业上可用的细胞松弛素很少。拟议的细胞实验室研究组旨在通过在细胞松弛素的发现、化学合成、生物工程、细胞生物学、体内和体外生物化学、植物和生态生物活性方面的专业知识的小组之间的系统和综合合作项目来解决这些问题。它的目标是能够应用现代合成化学(Kalesse，Klahn)和合成生物学(COX)来快速创造已知的和新的细胞松弛素。还将系统地结合特定的化学修饰，以产生具有新功能的细胞松弛素(即新的分子工具)。这些化合物将被系统地收集到化合物库中，并在体内和体外进行测试(Stradal，Rottner，Stadler，Zeilinger)，并用于探索它们的作用机制。同时，从真菌中发现新的细胞松驰剂(及其生物合成基因)也将是重要的(Stadler)，而研究植物对细胞松弛剂挑战的反应(Franke，Hildebrandt)将为生态学研究开辟新的途径。同时，Beemelmanns将研究细胞松弛菌在真菌/细菌/昆虫群落中的生态作用。此外，斯塔德勒集团运营着一个非常成功的(几乎是唯一的)放大平台，用于批量生产和提纯高达100克规模的天然产品。总体而言，将有八个高质量的个人项目，这些项目本身是前沿的，但具有非常高的项目间协作水平。至关重要的是，创建一个经过管理的复合库(Stadler)，将是一个支撑技术平台，将实现有效的合作，并允许RU追求在单个项目中无法实现的多学科长期目标。

Cytochalasans are natural products produced by fungi which have many potent biological activities. They bind strongly to actin and thus significantly effect eukaryotic cells. They also display remarkable bioactivities in prokaryotes and as anti-viral compounds where actin cannot be the target. They inhibit protein synthesis, sugar transport, plant growth, tumor necrosis factor and angiogenesis and are involved in immunosuppression and virulence and avirulence of fungi towards plants and insects, although most molecular mechanisms underlying these processes are unknown. Cytochalasans are constructed from amino acids and polyketides and they are often oxidatively tailored. Many hundreds of family members are known, but very few systematic investigations of structure activity relationships have been reported because very few cytochalasans are commercially available. The proposed CytoLabs Research Unit aims to address these problems through a systematic and integrated collaborative project between groups with expertise in the discovery, chemical synthesis, bioengineering, cell biology, in vivo and in vitro biochemistry, in planta and ecological bioactivity of cytochalasans. It aims to be able to apply modern synthetic chemistry (Kalesse, Klahn) and synthetic biology (Cox) to rapidly create known and new cytochalasans. Specific chemical modifications will also be systematically incorporated to generate cytochalasans with new functionality (i.e. new molecular tools). These compounds will be systematically collected into a compound library and tested in vivo and in vitro (Stradal, Rottner, Stadler, Zeilinger) and used to probe their mechanisms of action. Meanwhile, discovery of new cytochalasans (and their biosynthetic genes) from fungi will also be important (Stadler), while studying plant responses to cytochalasan challenge (Franke, Hildebrandt) will open new avenues of ecological research. In parallel Beemelmanns will investigate the ecological role of cytochalasans in fungal/bacterial/insect communities. In addition the Stadler group runs a highly successful (and almost unique) scale-up platform for the bulk production and purification of natural products at up to 100 gram scale. Overall there will be eight high quality individual projects which are themselves leading-edge, but with a very high level of inter-project collaboration. Crucially, the creation of a curated compound library (Stadler), will be an underpinning technology platform which will enable effective collaboration and allow the RU to pursue multi-disciplinary long-term goals which are unachievable in single projects.