Phase separation and RNA processingas drivers of cancer and neurodegenerative disease

下一代测序已经确定了至少50%缺乏可行治疗的突变。许多 这些突变蛋白质或与之相互作用的蛋白质被认为是癌症的关键驱动因素， 在转录调节和/或RNA加工中起作用。有趣的是， 也成为神经发育和病理学的重要特征。这表明有趣的是 肿瘤细胞和神经系统细胞对剪接机制的依赖性之间的相似之处。在 大脑，精心控制的选择性剪接导致神经系统发育，并可能 神经变性在肿瘤中，失调的可变剪接导致疾病。的共性 剪接，发展和癌症之间的联系可能存在于相分离的核体中， 提出调节RNA加工中的多个步骤。核小体（NB;核斑点，Cajal 机构等）可以与特定的细胞功能，如剪接，但不像细胞器， 封闭在脂质膜内，NB的功能取决于蛋白质和核酸的组装 没有膜结合的细胞。这个会议的想法是基于RNA的关键重要性而产生的， 沿着癌症和神经生物学的处理，以及来自患者肿瘤的数据， 存在和治疗无效。大多数癌症生物学家不了解蛋白质相互作用的生物物理学 以及对这些相互作用的深入了解，这些相互作用可能会推动新的靶向治疗的产生。的事实 RNA加工是肿瘤和神经元生物学的组成部分， 理解细胞中的相分离组合是创建这个多学科会议的原因。 本次会议有5个总体目标：（1）聚集疾病专家与RNA加工专家， （2）发展多学科研究，以促进对人类 生物学，（3）提供机会，种子多学科合作（4）支持培训生教育 关于和参与多学科科学，（5）催化新的科学发现，导致 针对人类疾病的其他不可操作的靶标的疗法。会议组织者包括： 博士Jeffrey Toretsky曾在多个级别的国家和国际会议上工作 包括美国临床肿瘤学会的儿科轨道椅。亚伦霍斯金斯博士 以前的经验，帮助组织项目的NSF资助的暑期学校，以及许多当地 两会几乎没有任何会议试图将这样一个明显的 医学/科学专业知识的多样性。如果没有这种性质的会议，目标研究人员群体 发展合作的可能性非常低。这次会议将作为一种酶， 催化这些相互作用，以促进科学和医学治疗。

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.