2014 DNA Topoisomerases in Biology and Medicine Gordon Research Conference

2014 DNA 拓扑异构酶在生物学和医学戈登研究会议

• 批准号: 8714782
• 负责人: MARY-ANN BJORNSTI
• 金额: $ 0.5万
• 依托单位: GORDON RESEARCH CONFERENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-10 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714782
• 关键词: ATP Hydrolysis; Academia; Alabama; Anti-Bacterial Agents; Antibiotics; Archaea; Bacterial DNA Topoisomerase I; Biology; Biophysics; Caliber; Cell physiology; Cellular biology; Chemotherapy-Oncologic Procedure; Collaborations; Complex; DNA; DNA Topoisomerases; Development; Discipline; Drug Targeting; Emerging Technologies; Ensure; Enzymatic Biochemistry; Enzymes; Eukaryota; Event; Fertilization; Free Energy; Funding; Genetic; Genomics; Goals; Human; Imagination; Imaging technology; Industry; Knowledge; Lead; Malignant Neoplasms; Medicine; Methods; Modeling; Molecular; Molecular Machines; Molecular Motors; Nature; Neurofibrillary Tangles; Organism; Pharmacology; Postdoctoral Fellow; Process; Prokaryotic Cells; Proteomics; Published Comment; Reporting; Research; Research Personnel; Role; Science; Scientist; Series; Stress; Students; Superhelical DNA; Techniques; Technology; Therapeutic Agents; Thinking; Topoisomerase; Universities; Virus; Work; antitumor agent; cancer therapy; chemotherapeutic agent; cytotoxic; insight; meetings; new technology; new therapeutic target; novel; novel strategies; novel therapeutics; public health relevance; single molecule; structural biology; symposium; therapeutic target

DESCRIPTION (provided by applicant): The helical nature of DNA causes a topological problem for its replication. Watson and Crick were well aware of this potential problem, and in 1953 they stated: "Since the two chains in our model are intertwined, it is essential for them to untwist if they are to separate... Although it is difficult at the moment to see how these processes occur without everything getting tangled, we do not feel that this objection will be insuperable". We now know that this problem is solved by the DNA topoisomerases, first reported in 1971 by James Wang with the discovery of bacterial topoisomerase I. Over the past ~40 years these enzymes have been found in all organisms (prokaryotes, eukaryotes, viruses and archaea) and to perform roles that are vital for survival, supporting replication, transcriptio and other processes where DNA topological problems need to be resolved. The enzymes are 'marvelous molecular machines' catalyzing the seemingly magical task of passing one piece of DNA through another to catalyze changes in DNA topology. Some of the enzymes are molecular motors, transducing the free energy of ATP hydrolysis into torsional stress in DNA (supercoiling). Although the outline of their mechanisms has been established, a great deal is unknown and emerging technologies, such as single-molecule methods, need to be applied to gain a deeper understanding of these enzymes and their roles in cellular processes. Topoisomerases have become key drug targets both for anti-bacterial and anti-cancer chemotherapy. This is due to their essential nature and their mechanism of action, which involves transient DNA cleavage that, if disrupted, can lead to highly cytotoxic events. Study of these enzymes in the context of myriad cellular processes is critical in research leading to the development of new chemotherapeutic agents. The inaugural 2014 DNA Topoisomerases in Biology and Medicine of Cancer Gordon Research Conference strives to attract scientists from a broad range of disciplines, highlighting recent advances in structural biology of topoisomerases and the application of single-molecule technologies to promote exciting new research on understanding topoisomerases at the detailed molecular level. At other end of the scale, advances in imaging technologies and proteomics/genomics enable new insights into the cellular roles of topoisomerases and their significance in human cancers. The meeting will be chaired by Prof. Tony Maxwell (John Innes Centre), with Dr. Mary-Ann Bjornsti (University of Alabama at Birmingham) as Vice Chair, both leaders in the topoisomerase field, representing bacterial enzymes and antibiotics, and eukaryotic enzymes and anti-tumor agents, respectively. This application seeks funds to support the participation of exceptionally talented young investigators (students, post-docs and fellows) from diverse backgrounds, to engage their imagination and interactions with leaders in the field. The informal nature of Gordon Research Conferences and the strong emphasis placed on high-caliber science presented with thought-provoking commentary ensures a highly interactive meeting to stimulate new perspectives on topoisomerases in biology and medicine.

描述（由申请人提供）：DNA的螺旋性质引起了复制的拓扑问题。沃森（Watson）和克里克（Crick）很清楚这个潜在的问题，并在1953年说：“由于我们模型中的两个链条是交织在一起的，因此，如果他们要分开的话，对于他们来说，对他们来说必须取消联系……尽管目前很难看到这些过程如何在没有一切纠缠的情况下出现，所以我们认为这种反对是不可能的。” We now know that this problem is solved by the DNA topoisomerases, first reported in 1971 by James Wang with the discovery of bacterial topoisomerase I. Over the past ~40 years these enzymes have been found in all organisms (prokaryotes, eukaryotes, viruses and archaea) and to perform roles that are vital for survival, supporting replication, transcriptio and other processes where DNA topological problems need to be解决。这些酶是“奇妙的分子机器”，它催化了将一个DNA通过另一种DNA传递以催化DNA拓扑的变化的看似神奇的任务。一些酶是分子电机，将ATP水解的自由能转化为DNA（超螺旋）中的扭转应力。尽管已经建立了其机制的轮廓，但是需要应用一些尚不清楚的技术，而新兴技术（例如单分子方法）需要更深入地了解这些酶及其在细胞过程中的作用。拓扑异构酶已成为抗菌和抗癌化疗的关键药物靶标。这是由于它们的本质性质及其作用机理，涉及瞬时DNA裂解，如果破坏，可能会导致高度细胞毒性事件。在多种细胞过程中对这些酶的研究对于导致新化学治疗剂的发展至关重要。 2014年首届DNA生物学和癌症戈登研究会议的DNA拓扑异构酶旨在吸引来自广泛学科的科学家，强调了拓扑异构酶结构生物学的最新进展，并应用单分子技术的应用，并应用了单粒分子技术的应用，以促进令人兴奋的新研究，以了解详细的肉眼毛细血管层面上的拓扑结构酶。在量表的另一端，成像技术和蛋白质组学/基因组学的进步使得对拓扑异构酶的细胞作用及其在人类癌症中的意义有了新的见解。这次会议将由托尼·麦克斯韦（Tony Maxwell）教授（约翰·内尼斯中心）主持，玛丽·安恩·比约恩斯蒂（Mary-Ann Bjornsti）（阿拉巴马大学的伯明翰大学）担任副主席，两位领导者都代表细菌性酶和抗生素，以及共同的抗生素，以及真度性的酶和抗肿瘤的食物。该申请寻求资金来支持来自不同背景的异常才华横溢的年轻调查员（学生，毕业后和研究员）的参与，以吸引他们的想象力和与该领域领导者的互动。戈登研究会议的非正式性质以及对高素质科学的强烈重视，发人深省的评论确保了一场高度互动的会议，以激发有关生物学和医学中拓扑异构体的新观点。