Coordination Funds

细胞chalasans是真菌产生的天然产物，具有许多有效的生物活性。它们与肌动蛋白结合强烈，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，并作为肌动蛋白不能作为目标的抗病毒化合物。它们抑制蛋白质合成、糖转运、植物生长、肿瘤坏死因子和血管生成，并参与免疫抑制和真菌对植物和昆虫的毒力和无毒作用，尽管这些过程的大多数分子机制尚不清楚。细胞chalasan是由氨基酸和聚酮构成的，它们通常是氧化定制的。数以百计的家族成员是已知的，但很少有系统的研究结构活性关系已被报道，因为很少的细胞chalasans是商业上可用的。拟议中的CytoLabs研究单位旨在通过一个系统和综合的合作项目，在发现、化学合成、生物工程、细胞生物学、体内和体外生物化学、植物和细胞chalasans的生态生物活性方面具有专业知识的小组之间解决这些问题。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chalasans。特定的化学修饰也将系统地结合以产生具有新功能的细胞chalasans（即新的分子工具）。这些化合物将被系统地收集到一个化合物库中，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chalasans（及其生物合成基因）也将是重要的（Stadler），而研究植物对细胞chalasan挑战的反应（Franke, Hildebrandt）将开辟新的生态学研究途径。beemelmann还将研究细胞chalasans在真菌/细菌/昆虫群落中的生态作用。此外，施泰德集团运营着一个非常成功的（几乎是独一无二的）规模化平台，用于批量生产和净化高达100克的天然产品。总的来说，将有8个高质量的独立项目，这些项目本身是领先的，但项目间的合作水平非常高。至关重要的是，创建一个精心策划的复合图书馆（Stadler），将成为一个基础技术平台，它将实现有效的协作，并允许RU追求单一项目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.