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出现拓扑问题。沃森和克里克很清楚这个潜在的问题，并在 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……虽然目前很难看出这些过程是如何在一切都纠缠在一起的情况下发生的，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可以通过 DNA 拓扑异构酶来解决，James Wang 于 1971 年首次报道了细菌拓扑异构酶 I。在过去的约 40 年里，这些酶已在所有生物体（原核生物、真核生物、病毒和古细菌）中被发现，并发挥着对生存至关重要的作用，支持复制、转录和其他需要解决 DNA 拓扑问题的过程。 解决了。这些酶是“奇妙的分子机器”，催化着看似神奇的任务，即让一段 DNA 穿过另一段，从而催化 DNA 拓扑结构的变化。一些酶是分子马达，将 ATP 水解的自由能转化为 DNA 中的扭转应力（超螺旋）。尽管其机制的轮廓已经确定，但仍有很多未知因素，需要应用单分子方法等新兴技术来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点。这是由于它们的本质及其作用机制，其中涉及短暂的 DNA 裂解，如果被破坏，可能会导致高度细胞毒性事件。在无数细胞过程中研究这些酶对于开发新化疗药物的研究至关重要。 首届 2014 年戈登癌症生物学和医学领域的 DNA 拓扑异构酶研究会议致力于吸引来自各个学科的科学家，重点介绍拓扑异构酶结构生物学的最新进展以及单分子技术的应用，以促进在详细的分子水平上了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重要性有了新的认识。会议将由 Tony Maxwell 教授（约翰·英尼斯中心）主持，Mary-Ann Bjornsti 博士（阿拉巴马大学伯明翰分校）担任副主席，两人都是拓扑异构酶领域的领导者，分别代表细菌酶和抗生素、真核酶和抗肿瘤药物。该申请寻求资金支持来自不同背景的才华横溢的年轻研究人员（学生、博士后和研究员）的参与，激发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以及对高水平科学的高度重视以及发人深省的评论确保了会议的高度互动，激发了生物学和医学中拓扑异构酶的新观点。