Sixth International Workshop on X-ray Damage to Biological Crystalline Samples

第六届生物晶体样品X射线损伤国际研讨会

• 批准号: 7916378
• 负责人: KEITH O HODGSON
• 金额: $ 0.7万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7916378
• 关键词: Back; Biocompatible Materials; Biological; Biology; Brain; Cancerous; Cells; Collaborations; Communities; Complex; Crystallography; Data; Development; Digestion; Disease; Drug Delivery Systems; Drug Design; Educational workshop; Electron Microscopy; Ensure; Exposure to; Food; Health; Human; Instruction; International; Ionizing radiation; Journals; Knowledge; Laboratories; Language; Lead; Life; Light; Metalloproteins; Methods; Movement; Muscle; Nucleic Acids; Oral; Participant; Peer Review; Physiologic pulse; Play; Process; Proteins; Public Health; Publishing; Radiation; Radiochemistry; Research; Research Personnel; Resolution; Roentgen Rays; Role; Sampling; Series; Shapes; Signal Transduction; Solutions; Source; Structural Models; Structure; Synchrotrons; Techniques; Time; X-Ray Crystallography; base; beamline; electron crystallography; improved; interest; macromolecule; planetary Atmosphere; posters; prevent; programs; public health relevance; radiation effect; research study; structural biology; synchrotron radiation; technique development; three dimensional structure; tool

DESCRIPTION (provided by applicant): Partial support is requested for The Sixth International Workshop on X-ray Damage to Biological Crystalline Samples to be held at the Stanford Synchrotron Radiation Light Source (SSRL) from March 11th -13th 2010. X-ray crystal diffraction is the best tool available to date to obtain a detailed atomic resolution three-dimensional structure of protein, nucleic acids and their complexes; knowledge of the structure is essential in order to understand their mechanism and modes of interaction, and provides an opportunity to modulate their activity in a way that is beneficial to human health. The development of modern synchrotron sources, which provide very intense X-ray beams, has had a dramatic impact on the number of target that can be tackled by this method, including medically important molecules and established or potential drug targets. However, continuous exposure to such intense X-rays during the experiment can cause significant damage to the crystalline sample, either preventing successful structural solution or compromising the biological information extracted from the structure. The International Workshops on X-ray Damage to Biological Crystalline Samples are the main forum for the presentation of the latest experiments and advances in understanding the effects of ionizing radiation on crystalline biological materials. The objectives of the Workshops are to further the detailed knowledge of radiation damage processes in macromolecular crystals, and to encourage the development of new techniques to mitigate or correct for the effects of damage on diffraction data and the resulting structural model. Some of the presentations are published as peer-reviewed articles in special issues of the Journal of Synchrotron Radiation. This practice ensures wider dissemination and provides a strong basis for intelligent use of synchrotron X-ray beamlines for structural biology studies. The program for Sixth Workshop in the series will be organized by a scientific committee composed of leaders in this research field. Session topics will include reduction and mitigation of radiation damage, radiation chemistry and radiolysis of biological molecules, progress in the understanding of radiation damage in biological crystallography, correcting for the effects of radiation damage, reduction of metalloproteins, the use of radiation damage to study macromolecular function of crystalline proteins, radiation damage in electron microscopy and electron crystallography, non-crystallographic methods to study radiation damage and the use of intense short pulsed X-ray sources, which are currently coming on line. PUBLIC HEALTH RELEVANCE (provided by the applicant): Proteins play a vital role in biology in that they are responsible for the machinery of life: e.g. digestion of food, signaling in the brain, movement of muscles etc. By finding their three-dimensional shape by X-ray crystallography, we are able to gain valuable information on their mechanism of action, and also to understand how and why they malfunction (e.g. by switching a cell from its normal state into a cancerous state), knowledge that informs drug design against disease and can lead eventually to better treatments to improve human health. However, the X-rays disrupt atomic bonds within and between the molecules of interest, which can result in failed experiments or in misleading structures. The Sixth International Workshop on X-ray Damage to Biological Crystalline Samples seeks to advance the understanding of the effects of X-rays on biological macromolecules and to apply this knowledge to the development of techniques to mitigate or correct these effects.

描述（由申请人提供）：请求部分支持将于2010年3月11日至13日在斯坦福同步辐射光源（SSRL）举行的第六届生物晶体样品X射线损伤国际研讨会。X射线晶体衍射是迄今为止获得蛋白质、核酸及其复合物的详细原子分辨率三维结构的最佳工具；了解其结构对于理解其机制和相互作用模式至关重要，并提供了以有益于人类健康的方式调节其活动的机会。现代同步加速器源的发展可提供非常强的 X 射线束，对通过这种方法可以处理的靶标数量产生了巨大影响，包括医学上重要的分子和已建立或潜在的药物靶标。然而，在实验过程中连续暴露于如此强烈的 X 射线可能会对晶体样品造成严重损坏，要么阻止成功的结构解析，要么损害从结构中提取的生物信息。 X 射线对生物晶体样品损伤国际研讨会是介绍最新实验和了解电离辐射对晶体生物材料影响方面进展的主要论坛。研讨会的目的是进一步了解大分子晶体辐射损伤过程的详细知识，并鼓励开发新技术以减轻或纠正损伤对衍射数据和所得结构模型的影响。一些演讲作为同行评审文章发表在《同步辐射杂志》的特刊上。这种做法确保了更广泛的传播，并为结构生物学研究中同步加速器 X 射线束线的智能使用提供了坚实的基础。该系列第六次研讨会的计划将由该研究领域的领导者组成的科学委员会组织。会议主题将包括减少和减轻辐射损伤、辐射化学和生物分子的辐射分解、生物晶体学中辐射损伤的理解进展、校正辐射损伤的影响、金属蛋白的减少、利用辐射损伤研究晶体蛋白的大分子功能、电子显微镜和电子晶体学中的辐射损伤、研究辐射损伤的非晶体学方法 以及使用目前即将上线的强短脉冲 X 射线源。 公共卫生相关性（由申请人提供）：蛋白质在生物学中发挥着至关重要的作用，因为它们负责生命机制：例如。食物的消化、大脑中的信号传导、肌肉的运动等。通过 X 射线晶体学发现它们的三维形状，我们能够获得有关其作用机制的有价值的信息，并了解它们如何以及为何发生故障（例如，通过将细胞从正常状态转变为癌性状态），这些知识为针对疾病的药物设计提供信息，并最终可以导致更好的治疗方法以改善人类健康。然而，X 射线会破坏感兴趣分子内部和之间的原子键，这可能会导致实验失败或产生误导性的结构。第六届 X 射线对生物晶体样品损伤国际研讨会旨在增进对 X 射线对生物大分子影响的理解，并将这些知识应用于开发减轻或纠正这些影响的技术。