Spatio-Temporal Organization of Chromatin and Information Transfer in Cancer

 描述(申请人提供)：这项申请是围绕着“染色质时空组织与癌症信息传递”的框架进行组织的。CR-PSOC的组织框架整合了化学、遗传学和物理学的优势，以解决癌症中的染色质动力学问题。通过使用共享模型系统，中心的研究人员将能够整合来自不同项目的数据，以对癌症中染色质物理重排的潜在机制以及如何控制基因表达产生新的概念性理解。该中心由三个相互关联的项目领域组成，每个领域都侧重于染色质结构和功能的不同方面。每个项目都结合了新兴的物理科学方法和分子和癌细胞生物学工具，以及物理科学的理论和建模方法，以实现对染色质机制、表观遗传调控途径、基因表达和癌症核环境的放松调控的定量和预测性了解。该中心的项目保持了明确的癌症重点，植根于了解癌症，特别是血液恶性肿瘤中染色质调节基因变化背后的分子机制。CR-PSOC的科学活动将得到两个共享资源核心的支持：纳米细胞测量核心和PDX人类肿瘤模型核心。这些核心将包含独特的资源，这些资源不仅将使CR-PSOC调查员受益，而且将大大增强整个PSON调查员的工具和方法。拟建的芝加哥地区-物理科学肿瘤学中心(CR-PSOC)汇集了物理科学、化学生物学和遗传学专业知识，并将这些专业知识与尖端分析仪器、专业测序技术、超高分辨率成像方式和新型癌症模型系统结合在一起。这种专业知识和资源的结合将使中心研究人员和PSO网络的成员能够以前所未有的深度和广度研究癌症中染色质和核动力学的结构和功能方面。CR-PSOC将提供一系列旨在激发在物理科学和肿瘤学前沿工作的下一代研究人员的兴趣和能力的教育活动和计划。通过将患者倡导者整合到中心管理中，并在建议和支持CR-PSOC发现的转换方面发挥关键作用，中心将稳定地关注通过基础研究的进步来确定临床结果的重要性。

 DESCRIPTION (provided by applicant): This application is organized around the framework of "Spatio-Temporal Organization of Chromatin and Information Transfer in Cancer". The organizing framework of the CR-PSOC integrates the strengths of chemistry, genetics, and physics to address chromatin dynamics in cancer. Through the use of shared model systems Center investigators will be able to integrate data from across projects to develop a new conceptual understanding of the mechanisms underlying physical rearrangement of chromatin in cancer and how that controls gene expression. The Center is composed of three interrelated project areas, each focused on different aspects of chromatin structure and function. Each project integrates emerging physical science approaches and molecular and cancer cell biology tools, as well as theory and modeling methods from the physical sciences, to achieve a quantitative and predictive understanding of the of deregulation of chromatin mechanics, epigenetic regulatory pathways, gene expression, and the nuclear environment in cancer. The Center's projects maintain a clear cancer focus rooted in understanding the molecular mechanism behind genetic alterations in chromatin regulators in cancer, particularly hematological malignancy. The scientific activities of the CR-PSOC will be supported by two shared resource cores: the Nanocytometry Core and the PDX Human Tumor Model Core. These cores will encompass unique resources that will not only benefit CR-PSOC investigators but will substantially augment the tools and approaches of investigators across the PSON. The proposed Chicago Region-Physical Science Oncology Center (CR-PSOC) brings together a unique constellation of physical science, chemical biology, and genetics expertise and couples this expertise with cutting edge analytical instrumentation, specialized sequencing technology, super high resolution imaging modalities, and novel cancer model systems. This combination of expertise and resources will enable Center investigators and members of the PSO Network to examine the structural and functional aspects of chromatin and nuclear dynamics in cancer at unprecedented depth and breadth. The CR-PSOC will provide a range of educational activities and programs designed to stimulate the interest and enhance the capabilities of the next generation of researchers working at the frontiers of physical science and oncology. Through integration of a patient advocate into Center administration with a key role in advising and supporting the translation of CR-PSOC discoveries the Center will maintain a steady focus on the importance of targeting clinical outcomes through advances in basic research.