Coordination Funds

在这个后基因组时代，人们认识到大量和多样化的转录产物来自非蛋白质编码的基因组。虽然我们现在知道这些无数的非编码RNA(NcRNA)转录本为细胞生理学贡献了复杂的调节层，但我们对RNA/RBP引导的基因表达调节(R3oGE)的知识远未被纳入我们的癌症诊断和治疗标准。癌症是德国第二大常见死因，发病率不断上升。因此，对新的治疗概念有很高的需求，特别是对于患者预后不佳的恶性肿瘤。目前的癌症研究和治疗努力主要集中在蛋白质编码基因上，主要是催化和受体蛋白质。然而，组学技术的进步加速了1500多个RNA结合蛋白(RBPs)的鉴定，并不断增加ncRNAs的数量。这造成了一种情况，即新的ncRNAs和RBPs的发现超过了它们在肿瘤发生中的功能描述-导致不断增加的知识差距，限制了我们开发针对R3oGE的治疗的效率。拟议的“焦点RNA”研究单位(RU5433)将通过研究ncRNAs和限制性商业惯例在癌症中的作用和治疗靶点潜力来解决这一知识差距。因此，RIF-RU的最终目标是通过了解潜在的生物学原理和评估临床前环境中的新策略来评估和开发以RNA为中心或R3oGE指导的治疗概念。为了实现这一目标，我们计划将疾病相关机制的基础研究--用于新的靶标识别--与靶标验证研究相结合，直至面向临床前的药物开发和测试。因此，虽然不同项目的癌症实体不同，但它们通过共同的研究目标、所研究的分子决定因素和机制以及实现各自目标的技术/方法/研究平台联系在一起。总的来说，参与的研究人员提供了一个多学科框架，包括补充工具和动物模型，这些工具和动物模型对于在分子和细胞水平以及在小鼠肿瘤模型中解开R3oGE的生理相关机制至关重要。为了从长远的角度建立一个转译研究联盟，一些参与的研究人员进一步启动了临床前研究，以探索研究良好的R3oGE分子决定因素的治疗靶向，并开发针对这些分子决定因素的治疗概念。这些合作努力将促进针对癌症中异常R3oGE治疗潜力的研究，预计将为患者和整个社会带来好处。

In this post-genomics era, it is recognized that an enormous number and diversity of transcriptional products arise from the none protein-coding genome. While we now know that these myriad non-coding RNA (ncRNA) transcripts contribute complex layers of regulation to cellular physiology, our knowledge of RNA/RBP-guided Regulation of Gene Expression (R3oGE) is far from being incorporated into our standards of diagnosis and treatment of cancer. Cancer is the second most common cause of death in Germany with increasing prevalence. Accordingly, there is high demand for novel therapeutic concepts, in particular for malignancies of dismal patient outcome. Current cancer research and treatment efforts mainly focus on protein-coding genes, largely catalytic and receptor proteins. However, technical advances in omics technologies have expedited the identification of over 1500 RNA-binding proteins (RBPs) and a continuously growing number of ncRNAs. This poses a situation in which the discovery of new ncRNAs and RBPs outstrips their functional characterization in oncogenesis – leading to a constantly increasing knowledge gap that limits our efficiency in developing therapies targeting the R3oGE. The proposed “RNA in focus” Research Unit (RU5433) will address this knowledge gap by investigating the role and therapeutic target potential of ncRNAs and RBPs in cancer. Accordingly, the ultimate aim of the RIF-RU is to evaluate and develop RNA-centered or R3oGE-directed therapeutic concepts by understanding the underlying biology, and evaluating novel strategies in pre-clinical context. Towards this aim, we plan to combine basic research on disease-associated mechanisms – for novel target identification – with research on target validation up to pre-clinically-oriented drug development and testing. Hence, while the cancer entity differs between projects, they are connected by a common research goal, molecular determinants and mechanisms studied, and techniques/methods/research platforms to achieve the respective aims. Collectively, the participating investigators provide a multidisciplinary framework of complementary tools and animal models that are essential for unraveling physiologically relevant mechanisms of R3oGE at the molecular and cellular level as well as in murine tumor models. Towards establishing a translational research consortium in the long-term perspective, some participating investigators furthermore initiated pre-clinical studies to explore the therapeutic targeting of well-studied molecular determinants of R3oGE and develop therapeutic concepts to target these. These collaborative efforts will promote research on the therapeutic potential of targeting aberrant R3oGE in cancer, with projected benefits for patients and society as a whole.