FASEB SRC on Dynamic DNA Structures in Biology

FASEB SRC 关于生物学中动态 DNA 结构

• 批准号: 8782146
• 负责人: SERGEI MIRKIN
• 金额: $ 0.9万
• 依托单位: FEDERATION OF AMER SOC FOR EXPER BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782146
• 关键词: Adopted; Aging; Antigenic Switching; Area; Belief; Biology; Chromosomal Rearrangement; Chromosome Fragility; Collaborations; DNA; DNA Sequence; DNA Structure; Development; Disease; Employee Strikes; Fostering; Genetic Processes; Genetic Recombination; Genetic Transcription; Genome; Genomic DNA; Genomics; Gymnastics; Hand; Health; Heart; Hereditary Disease; Human; Illinois; Immune response; Inherited; Investigation; Knowledge; Lead; Left; Light; Maintenance; Malignant Neoplasms; Molecular Conformation; Mutagenesis; Nanotechnology; Neurologic; Nuclear; Participant; Pathology; Play; Postdoctoral Fellow; Process; Property; Recurrence; Regulation; Request for Proposals; Research; Research Personnel; Resolution; Role; Science; Scientist; Side; Structure; Students; Transcriptional Activation; career; human disease; interest; meetings; nano; novel; novel diagnostics; novel strategies; novel therapeutics; physical property; posters; programs; public health relevance; symposium; therapeutic target

DESCRIPTION (provided by applicant): This proposal requests partial support for the FASEB Summer Research Conference on Dynamic DNA Structures in Biology, to be held at Itasca, Illinois, July 20-25, 2014. For decades after its discovery, DNA was believed to be a rigid, right-handed double helix. This belief was shaken by the findings that DNA structure is much more dynamic. In fact, DNA can form an enormous variety of conformations, including cruciform-like, left-handed helixes, three and four stranded helices, slip-stranded configurations, etc. Most importantly, repetitive DNA sequences, which are overrepresented in genomic DNA, are particularly prone to structural transitions. Transient denaturation of the double helix, which promotes these dynamic transitions in DNA structure, occurs during all major DNA transactions, including replication, transcription, and recombination. Studies conducted in many labs worldwide have confirmed that structure-prone DNA sequences are central to the normal functioning of the genome, and they are also responsible for its occasional malfunctioning. One particularly striking example is the discovery that expansions of structure-prone DNA repeats leads to more than thirty hereditary neurological and developmental diseases in humans. Dynamic DNA structures are also associated with translocations observed in many human cancers. They are also involved in regular DNA processes including transcriptional activation, regulation of antigenic switching, and DNA recombination essential to the immune response. In an unexpected twist, these DNA structures appeared to be invaluable for nanotechnology, where their unusual physical properties find numerous applications. The long-term objective of this Conference is to enhance our understanding of how dynamic DNA structures form, how they are resolved, how they contribute to normal genetic processes and to pathological developments, including genetic disease, cancer and aging. The specific aims are to explore current understanding, to identify new avenues of investigation, to define novel mechanisms that promote formation and resolution of dynamic DNA structures and, thus, offer therapeutic targets for maintenance of genomic integrity, to stimulate collaborations, and to foster the long-term development of this area by promoting participation of junior scientists. To that end, we will convene 33 speakers and discussion leaders and more than 100 participants for five intense and highly interactive days of science. The program will include a keynote and eight sessions, entitled: (1) Expandable DNA Repeats and Human Disease; (2) Chromosomal Fragility; (3) Transcription and Its Collisions with Replication; (4) Repeat-Induced Mutagenesis; (5) DNA Gymnastics in Recombination; (6) Recurrent and Non- Recurrent Chromosomal Rearrangements in Human Disease; (7) G4 DNA in the Genome; (8) Nano-DNA Structures. Each session will include two-to-four short talks by students, postdocs, and newly independent investigators, and three afternoon poster sessions will permit the attendees to present and discuss their newest results. The significance of this conference is that it uniquely propels research by bringing together investigators with a common focus but varied backgrounds, expertise and experimental approaches, thus, enabling research to progress more rapidly. The biomedical relatedness is in the importance of dynamic DNA structures in normal nuclear functions and as the cause of genomic pathologies that result in genetic disease.

描述（由申请人提供）：本提案要求对将于 2014 年 7 月 20 日至 25 日在伊利诺伊州伊塔斯卡举行的关于生物学动态 DNA 结构的 FASEB 夏季研究会议提供部分支持。在其发现后的几十年里，人们相信 DNA是刚性的右手双螺旋。 DNA 结构更具动态性的发现动摇了这种信念。事实上，DNA 可以形成各种各样的构象，包括十字形、左手螺旋、三链和四链螺旋、滑链构型等。最重要的是，在基因组 DNA 中出现过多的重复 DNA 序列特别容易发生结构性转变。双螺旋的瞬时变性会促进 DNA 结构中的这些动态转变，发生在所有主要 DNA 事务中，包括复制、转录和重组。世界各地许多实验室进行的研究已经证实，易于结构的 DNA 序列对于基因组的正常功能至关重要，并且也是基因组偶尔出现故障的原因。一个特别引人注目的例子是，我们发现，易于结构的 DNA 重复序列的扩展会导致人类 30 多种遗传性神经系统和发育疾病。动态 DNA 结构也与许多人类癌症中观察到的易位有关。它们还参与常规 DNA 过程，包括转录激活、抗原转换调节以及免疫反应所必需的 DNA 重组。出人意料的是，这些 DNA 结构对于纳米技术似乎具有无价的价值，它们不寻常的物理特性在纳米技术中得到了广泛的应用。 本次会议的长期目标是加深我们对动态 DNA 结构如何形成、如何分解、如何促进正常遗传过程和病理发展（包括遗传病、癌症和衰老）的理解。具体目标是探索当前的理解，确定新的研究途径，定义促进动态 DNA 结构形成和解析的新机制，从而为维持基因组完整性提供治疗靶点，刺激合作，并促进通过促进初级科学家的参与来促进该领域的长期发展。为此，我们将 召集 33 名演讲者和讨论领袖以及 100 多名参与者，进行为期五天紧张且高度互动的科学活动。该计划将包括一场主题演讲和八场会议，主题为：(1) 可扩展 DNA 重复序列与人类疾病； (2)染色体脆性； (3)转录及其与复制的碰撞； (4)重复诱导突变； (5) 重组中的DNA体操； (6) 人类疾病中的复发性和非复发性染色体重排； (7) 基因组中的G4 DNA； (8) 纳米 DNA 结构。每场会议将包括由学生、博士后和新独立研究人员进行的两到四次简短演讲，三场下午的海报会议将允许与会者展示和讨论他们的最新结果。 这次会议的意义在于，它通过将具有共同关注点但不同背景、专业知识和实验方法的研究人员聚集在一起来独特地推动研究，从而使研究能够更快地取得进展。生物医学相关性在于动态DNA结构在正常核功能中的重要性以及作为导致遗传病的基因组病理的原因。