eDyNAmiC - JACKSONLAB

动力 - JACKSONLAB

• 批准号: 10892537
• 负责人: Roel GW Verhaak
• 金额: $ 29.37万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-24 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10892537
• 关键词: Acceleration; Advocate; Affect; Architecture; Blood; Cancer Patient; Cells; Chemicals; Chemistry; Chromosome Pairing; Chromosomes; Collaborations; Communities; Computers; DNA; Data; Diagnostic; Drug Targeting; Drug resistance; Early Diagnosis; Education; Evolution; Family; Fingerprint; Fostering; Funding Mechanisms; Gene Expression Regulation; Gene Order; Generations; Genes; Genetic; Genetic Transcription; Genome; Human; Immune Evasion; Immune system; Immunobiology; Immunologics; Immunology; Immunotherapy; Infrastructure; International; Licensing; Ligands; Maintenance; Malignant Neoplasms; Medicine; Modeling; Monitor; Mutation; Nucleic Acids; Oncogenes; Patients; Pharmaceutical Preparations; Process; Productivity; Research Personnel; Resources; Role; Scientist; Therapeutic; Tissues; Tumor Promotion; Work; Yeast Model System; cancer genomics; cancer heterogeneity; cancer type; combinatorial; epigenomics; experience; extrachromosomal DNA; genome sequencing; innovation; insight; live cell imaging; machine learning algorithm; mathematical model; multiple omics; novel; prevent; programs; time use; tool; tumor; tumor growth; whole genome; yeast genetics

eDyNAmiC (extrachromosomal DNA in Cancer) Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumour-promoting genes can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). These ecDNA do not follow the normal “rules” of chromosomal inheritance, enabling tumours to achieve far higher levels of cancer-causing oncogenes than would otherwise be possible, and licensing cancers with a way to evolve and change their genomes to evade treatments at rates that would be unthinkable for human cells. The altered circular architecture of ecDNAs also changes the way that the cancer-causing genes are regulated and expressed, further contributing to aggressive tumour growth. These unique features make ecDNA-containing cancers especially aggressive and difficult to treat. Cancer patients whose tumours harbour ecDNA have markedly shorter survival. Despite being first seen over fifty years ago, the critical importance of ecDNA has only recently come to light, and the scale of the problem is substantial. ecDNAs are present in nearly half of all human cancer types and potentially up-to a third of all cancer patients. The collective current understanding of how ecDNA form, how they function, how they move around the cell, how they evolve to resist treatment, how they impact the immune system, and how they can be effectively targeted are lacking. We bring together an internationally recognized, pioneering interdisciplinary team of cancer biologists, geneticists, computer scientists, evolutionary biologists, mathematicians, clinicians, and patient advocates to boldly create novel insights and resources and to provide transformative solutions to one of Cancer’s Grand Challenges. A core team of experienced and productive ecDNA investigators will work with new investigators in the ecDNA and cancer fields to bring completely new perspectives and approaches to this daunting challenge. By bridging cutting-edge and diverse approaches and insights from cancer genomics, yeast genetics, epigenomics, artificial genome synthesis, longitudinal patient tracking, combinatorial and machine learning algorithms, mathematical modelling, immunobiology, and innovative chemistry we will develop a new understanding of the role of ecDNA in cancer, and we will find new ways to drug the undruggable. This bold programme, which consists of 7 work packages and a committed international infrastructure, generates new and unusual collaborations that would simply be impossible under any other type of funding mechanism. Our programme endeavours to foster bold innovative solutions to one of the hardest problems in cancer and to one of the greatest challenges facing cancer patients.

edyanic（癌症外DNA） 人类基因在23对染色体上排列，但是在癌症中，促进肿瘤的基因可以罚款并重新定位到圆形的，dna的圆形碎片（ECDNA）。伴有癌症的癌症水平比其基因组可能会以beuuman细胞的速度逃避治疗的可能性。尤其是在五十年前出现的侵略性和差异，eCDNA的重要性只会曝光，并且该问题的规模是近一半。 eCDNA形成的集体电流，如何围绕细胞的移动，进化处理如何影响免疫系统以及如何有效的有针对性的目标。进化生物学家，数学家和PA的倡导者倡导大胆的Createl Insights，并为一种癌症提供了一种变革性的解决方案从癌症基因组学，酵母遗传学，人工基因组，纵向患者跟踪，组合和机器学习算法，数学建模，eCDNA作用的免疫生物学G中桥接尖端，多样和见解，我们将发现吸毒的新闻这项大胆的计划包括7个工作包和国际核心基础设施，产生了新的和不寻常的合作一个一个一个一个最大的挑战性癌症患者。