Coordination Funds

协调基金

• 批准号: 510840465
• 负责人: Professor Dr. Stefan Hüttelmaier
• 金额: --
• 依托单位: Institut für Molekulare Medizin
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/510840465?language=en
• 关键词: Coordination; Funds

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.

在这个后基因组时代，人们认识到，大量和多样性的转录产物产生于非蛋白质编码基因组。虽然我们现在知道这些无数的非编码RNA（ncRNA）转录物对细胞生理学的调控有着复杂的作用，但我们对RNA/RBP引导的基因表达调控（R3 oGE）的了解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，患病率不断上升。因此，对于新的治疗概念，特别是对于患者结果令人沮丧的恶性肿瘤，存在很高的需求。目前的癌症研究和治疗工作主要集中在蛋白质编码基因，主要是催化蛋白和受体蛋白。然而，组学技术的技术进步已经加速了1500多个RNA结合蛋白（RBP）和不断增长的ncRNA数量的鉴定。这造成了一种情况，即新的ncRNA和RBP的发现超过了它们在肿瘤发生中的功能特征-导致不断增加的知识差距，限制了我们开发靶向R3 oGE的疗法的效率。拟议的“RNA焦点”研究单位（RU 5433）将通过研究ncRNA和RBP在癌症中的作用和治疗靶点潜力来解决这一知识缺口。因此，RIF-RU的最终目的是通过了解潜在的生物学和评估临床前背景下的新策略来评估和开发以RNA为中心或R3 oGE为导向的治疗概念。为了实现这一目标，我们计划将联合收割机的基础研究疾病相关的机制-新的目标识别-与目标验证的研究，直到临床前导向的药物开发和测试。因此，虽然癌症实体在项目之间存在差异，但它们通过共同的研究目标，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/研究平台联系起来。总的来说，参与的研究人员提供了一个多学科的补充工具和动物模型框架，这些工具和模型对于在分子和细胞水平以及小鼠肿瘤模型中揭示R3 oGE的生理相关机制至关重要。为了建立一个长期的转化研究联盟，一些参与研究的研究者进一步启动了临床前研究，以探索R3 oGE分子决定簇的治疗靶点，并开发针对这些决定簇的治疗概念。这些合作努力将促进针对癌症异常R3 oGE的治疗潜力的研究，预计将为患者和整个社会带来益处。