FASEB SRC on Dynamic DNA Structures in Biology

描述(由申请人提供)：本提案请求部分支持将于2014年7月20-25日在伊利诺伊州伊塔斯卡举行的FASEB生物学动态DNA结构夏季研究会议。在发现DNA后的几十年里，人们一直认为DNA是一个刚性的右旋双螺旋结构。DNA结构更具活力的发现动摇了人们的这一信念。事实上，DNA可以形成各种各样的构象，包括十字形、左旋螺旋、三链和四链螺旋、滑链构型等。最重要的是，重复的DNA序列在基因组DNA中过度表达，特别容易发生结构转变。在包括复制、转录和重组在内的所有主要DNA交易中，都会发生双螺旋的瞬时变性，从而促进DNA结构的这些动态转变。在世界各地的许多实验室进行的研究已经证实，易于结构的DNA序列是基因组正常功能的核心，它们也是基因组偶尔发生故障的原因。一个特别引人注目的例子是，发现易于结构的DNA重复序列的扩张导致人类30多种遗传性、神经系统和发育性疾病。动态DNA结构也与在许多人类癌症中观察到的易位有关。它们还参与常规的DNA过程，包括转录激活、调节抗原转换和免疫反应所必需的DNA重组。令人意想不到的是，这些DNA结构似乎对纳米技术来说是无价的，它们不同寻常的物理特性在纳米技术中有很多应用。本次会议的长期目标是加强我们对动态DNA结构如何形成、如何分解、它们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。其具体目的是探索当前的理解，确定新的研究途径，确定促进动态DNA结构形成和分解的新机制，从而为维持基因组完整性提供治疗靶点，促进合作，并通过促进初级科学家的参与促进该领域的长期发展。为此，我们将 召集33名演讲者、讨论领袖和100多名参与者，进行五天紧张和高度互动的科学活动。该计划将包括一场主题报告和八场会议，题为：(1)可扩展DNA重复序列与人类疾病；(2)染色体脆弱性；(3)转录及其与复制的碰撞；(4)重复诱导突变；(5)DNA重组；(6)人类疾病中的经常性和非经常性染色体重排；(7)基因组中的G4DNA；(8)纳米DNA结构。每个会议将包括两到四个由学生、博士后和新独立调查人员进行的简短演讲，三个下午的海报会议将允许与会者展示和讨论他们的最新成果。这次会议的意义在于，它以独特的方式推动研究，将具有共同重点但不同背景、专业知识和实验方法的研究人员聚集在一起，从而使研究能够更快地取得进展。生物医学的相关性在于动态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。

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.