Phase separation and RNA processingas drivers of cancer and neurodegenerative disease

下一代测序已经确定了至少50%缺乏可操作治疗的突变。许多. 这些突变的蛋白质，或它们相互作用的蛋白质，被确定为癌症和 在转录调控和/或RNA加工中的作用。有趣的是，监管良好的RNA处理 也成为神经发育和病理学的一个重要特征。这表明很有趣 肿瘤细胞和神经系统细胞对剪接机制的依赖之间存在相似之处。在 大脑，精心控制的选择性剪接导致神经系统发育，并有可能 神经退行性变。在肿瘤中，不受调控的选择性剪接会导致疾病。共同之处 剪接、发育和癌症之间的关系可能存在于相分离的核体中 提出了在RNA加工中调节多个步骤的建议。核体(国家安全局；核斑点，卡哈尔 身体等)可以与特定的细胞功能相关联，如剪接，但不同于细胞器 NBS被包裹在脂膜中，其功能依赖于蛋白质和核酸的组装 它们不是膜结合的。这个会议的想法是基于RNA的关键重要性而产生的 癌症和神经生物学的处理以及来自患者肿瘤的数据显示 存在和治疗无效。大多数癌症生物学家都不知道蛋白质相互作用的生物物理学。 对这些相互作用的洞察可能会推动新的靶向治疗的创造。事实是 RNA加工是肿瘤和神经生物学不可或缺的一部分，而且发生在这些糟糕的 了解细胞中的相分离组装是创建这次多学科会议的原因。 本次会议有5个总体目标：(1)召集疾病专家和RNA加工专家以及 相分离，(2)发展多学科研究，以促进对人类的理解 生物学，(3)提供多学科合作的机会(4)支持学员教育 关于和参与多学科科学，以及(5)催化新的科学发现，从而导致 针对人类疾病的其他不可操作的靶点的治疗。会议组织者包括： 杰弗里·托雷斯基博士，在多个级别的国内和国际会议上有经验 包括美国临床肿瘤学会的儿科跑道椅。亚伦·霍斯金斯博士 以前帮助组织NSF资助的暑期学校项目的经验以及许多当地 会议。几乎没有任何会议试图将这样一个明显的 医疗/科学专业知识的多样性。如果没有这种性质的会议，目标研究人员小组 发展合作的可能性非常低。这次会议将作为一种酶来 催化这些相互作用，以推动科学和医疗治疗。

Next-generation sequencing has identified at least 50% of mutations that lack actionable therapy. Many of these mutant proteins, or proteins they interact with, are being identified as key drivers of cancer and function in transcriptional regulation and/or RNA processing. Interestingly, well-regulated RNA processing has also emerged as a critical feature of neural development and pathology. This suggests interesting parallels between the reliance of both tumor and nervous system cells on the splicing machinery. In the brain, carefully controlled alternative splicing leads to nervous system development and potentially neurodegeneration. In tumors, disregulated alternative splicing leads to disease. The commonalities between splicing, development, and cancer may reside in phase-separated nuclear bodies that have been proposed to modulate multiple steps in RNA processing. Nuclear bodies (NBs; nuclear speckles, Cajal Bodies, etc..) can be associated with specific cellular functions, like splicing, but unlike organelles that are enclosed within lipid membranes, the function of NBs depends on assemblies of proteins and nucleic acids that are not membrane-bound. This conference idea arose based upon the critical importance of RNA processing in cancer and neurobiology along with data from patient tumors showing both a mutational presence and therapeutic void. Most cancer biologists are unaware of the biophysics of protein interactions and insights into these interactions that are likely to drive the creation of novel targeted therapy. The fact that RNA processing is integral to the tumor and neuronal biology and is occurring in these poorly understood phase-separated assemblages in cells is reason to create this multidisciplinary meeting. This meeting has 5 overall objectives: (1) Gather disease specialists with experts in RNA processing and phase separation, (2) Develop multi-disciplinary research as a vehicle to advance understanding of human biology, (3) Provide opportunities to seed multi-disciplinary collaborations (4) Support trainee education about and participation in multi-disciplinary science, and (5) Catalyze new scientific discoveries that lead to therapies against otherwise non-actionable targets of human disease. The conference organizers include: Dr. Jeffrey Toretsky who has had experience at multiple levels of national and international conferences including the pediatric track chair at the American Society of Clinical Oncology. Dr. Aaron Hoskins has previous experience helping to organize programs for a NSF-funded summer school as well as many local conferences. There are virtually no conferences that have attempted to bring together such an apparent diversity of medical/scientific expertise. Without a meeting of this nature, the targeted groups of researchers would have a very low likelihood of developing collaborations. This conference will act as an enzyme to catalyze those interactions in order to advance science and medical therapies.