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.
(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.
