Coordination Funds

协调基金

• 批准号: 507937508
• 负责人: Professor Dr. Argyris Papantonis
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/507937508?language=en
• 关键词: Coordination; Funds

Eukaryotic genomes encode the information that defines both general and specific characteristics of each cell type. However, the linear DNA sequence alone often fails to predict cellular functions and phenotypic outcomes. In fact, genomic information is modified and regulated by a number of additional layers of gene expression control. One of these, the spatial folding of chromosomes, has been recently identified as a critical such layer. Spatial chromosomal folding is established through binding of transcription factors as well as via epigenetic mechanisms and biophysical forces that act in a concerted manner to regulate gene expression in space and time. Therefore, studying the principles of three-dimensional chromatin folding allow us to unravel its contribution in gene regulation during development and disease. The primary goal of this Priority Program is to dissect the structure-to-function relationship of the genomes of higher metazoans at high spatiotemporal resolution in study systems relevant to genome integrity, development, and disease. Aside from the apparent goal of bringing together a critical mass of German-academia groups engaged in this line of research, we also aspire to host projects in this SPP that undertake in vitro and in vivo functional and mechanistic studies on model organisms and human samples that can deepen our understanding of how genome architecture underlies cell and tissue physiology. All projects (collaborative or standalone) should have a clear and substantial focus on mechanisms and forces driving or maintaining 3D chromatin folding and its role in gene regulation. A combination of advanced molecular methods, super‐resolution and/ or live‐cell imaging, precision genetic editing, and novel computational tools is envisaged. Thus, projects included in this 2nd SPP funding period should: (i) develop and apply novel technologies that can capture spatial chromatin conformation, also in conjunction with other genomic features (e.g., transcription, histone modifications, DNA methylation), to resolve and track features of genomic architecture in the nucleus down to the single cell-level; (ii) dissect the functional impact of 3D chromatin folding on gene expression or genome integrity in vitro and in vivo during development or cell differentiation; (iii) causally connect 3D chromatin folding with disease etiology via precision genome editing and patient data and/or disease models; (iv) develop and apply novel computational approaches allowing us to integrate, quantitatively model, and visualize the end-effects and dynamics of spatial genome organization. In the end, we aspire that the consortium will generate new knowledge bringing us closer to defining a parsimonious set of rules that explain the structure-to-function relationship of eukaryotic chromosomes.

真核基因组编码的信息定义了每种细胞类型的一般特征和特定特征。然而，仅线性 DNA 序列通常无法预测细胞功能和表型结果。事实上，基因组信息受到许多额外的基因表达控制层的修改和调节。其中之一，染色体的空间折叠，最近被认为是一个关键的层。空间染色体折叠是通过转录因子的结合以及表观遗传机制和生物物理力建立的，这些机制和生物物理力以协调一致的方式调节空间和时间上的基因表达。因此，研究三维染色质折叠的原理使我们能够揭示其在发育和疾病过程中基因调控中的贡献。该优先计划的主要目标是在与基因组完整性、发育和疾病相关的研究系统中以高时空分辨率剖析高等后生动物基因组的结构与功能关系。除了将参与这一领域研究的德国学术界团体聚集在一起的明显目标外，我们还渴望在这个 SPP 中主持项目，对模型生物体和人类样本进行体外和体内功能和机制研究，以加深我们对基因组结构如何构成细胞和组织生理学的理解。所有项目（合作或独立）都应明确且实质性地关注驱动或维持 3D 染色质折叠的机制和力量及其在基因调控中的作用。设想将先进的分子方法、超分辨率和/或活细胞成像、精确基因编辑和新颖的计算工具结合起来。因此，第二个 SPP 资助期中包含的项目应该：（i）开发和应用能够捕获空间染色质构象的新技术，并结合其他基因组特征（例如转录、组蛋白修饰、DNA 甲基化），以解析和跟踪细胞核中基因组结构的特征，直至单细胞水平； (ii) 剖析发育或细胞分化过程中体外和体内 3D 染色质折叠对基因表达或基因组完整性的功能影响； (iii) 通过精确的基因组编辑和患者数据和/或疾病模型将 3D 染色质折叠与疾病病因学因果联系起来； (iv) 开发和应用新颖的计算方法，使我们能够整合、定量建模和可视化空间基因组组织的最终效应和动态。最后，我们希望该联盟能够产生新的知识，使我们更接近于定义一套简洁的规则来解释真核染色体的结构与功能关系。