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的螺旋性质导致其复制的拓扑问题。沃森和克里克很清楚这个潜在的问题，他们在1953年表示：“由于我们模型中的两条链是交织在一起的，如果它们要分开，就必须解开它们。虽然目前很难看到这些过程是如何发生的，而一切都没有纠缠在一起，但我们并不认为这种反对意见是不可克服的。我们现在知道这个问题是由DNA拓扑异构酶解决的，1971年James Wang首次报道了细菌拓扑异构酶I的发现。在过去的~40年中，这些酶已在所有生物体（原核生物、真核生物、病毒和古细菌）中发现，并发挥对生存至关重要的作用，支持复制、转录和需要解决DNA拓扑问题的其他过程。这些酶是“奇妙的分子机器”，催化着一段DNA通过另一段DNA催化DNA拓扑结构变化的看似神奇的任务。一些酶是分子马达，将ATP水解的自由能转换为DNA中的扭转应力（超螺旋）。虽然它们的机制的轮廓已经建立，但有很多是未知的，需要应用新兴技术，如单分子方法，以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。这是由于它们的基本性质和作用机制，其涉及瞬时DNA切割，如果被破坏，可能导致高度细胞毒性事件。在无数细胞过程的背景下对这些酶的研究在导致新的化疗剂的开发的研究中是至关重要的。 首届2014年DNA拓扑异构酶在生物学和癌症医学戈登研究会议努力吸引来自广泛学科的科学家，突出拓扑异构酶的结构生物学的最新进展和单分子技术的应用，以促进在详细的分子水平上理解拓扑异构酶的令人兴奋的新研究。另一方面，成像技术和蛋白质组学/基因组学的进步使人们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认识。会议将由Tony麦克斯韦教授（John Innes中心）主持，Mary-Ann Bjornsti博士（伯明翰的亚拉巴马大学）担任副主席，他们都是拓扑异构酶领域的领导者，分别代表细菌酶和抗生素以及真核酶和抗肿瘤剂。该申请寻求资金，以支持来自不同背景的非常有才华的年轻调查人员（学生，博士后和研究员）的参与，以发挥他们的想象力并与该领域的领导者互动。戈登研究会议的非正式性质和对高素质科学的高度重视，并提供发人深省的评论，确保了高度互动的会议，以激发生物学和医学中拓扑异构酶的新观点。