Joint Center for Structural Genomics

描述（由申请人提供）：结构基因组学联合中心（JCSG）的目标是参与NIGMS PSI：生物学计划，作为高通量结构测定中心。在过去十年中组装的JCSG高通量（HT）平台将通过X射线晶体学和NMR在从细菌到人类的广泛目标上有效地向社区提供大量蛋白质结构，包括具有挑战性的目标，如真核蛋白质，蛋白质-蛋白质和其他大分子复合物。在整个PSI：生物学，JCSG将适应和调整其业务，以实现其成长和发展的计划目标。JCSG将继续开发新的技术和方法，包括实验和计算，以解决将提出的目标范围，同时将每个结构的成本保持在最低水平，质量达到最高标准。PSI网络内的整合将是一个高度优先事项，包括与生物学合作中心，未来的PARS和社区的互动，以及对所有PSI网络活动的支持，包括PSI-SGKB和PSI-MR。JCSG将利用其丰富的经验，制定最佳策略，以提高成功的机会，消除那些导致失败的机会。通过明智地选择目标，将促进对扩展蛋白质宇宙的结构覆盖的原始PSI使命的贡献，以及从结构角度促进单个生物体或细胞的整个网络、通路和分子机制的解剖的工具和合作的开发。生物医学主题项目将侧重于人类微生物组。肠道细菌与人体的相互作用是深刻的，并且对维持一般人类健康具有显著影响，但也与肥胖症、炎性疾病、糖尿病和某些癌症相关，仅举几例。JCSG将利用其HT平台，通过与其他PSI：生物学参与者合作进行广泛的生物物理，功能和生物信息学分析，促进其所有结构的生物学和生物医学影响。因此，总体目标是提供一个强大的，灵活的HT结构测定平台，将迎接挑战，并拥抱来自PSI的项目产生的新机遇：生物学伙伴关系和其他PSI支持的项目。此外，我们将努力沿着PSI网络，促进PSI资源、材料、方法、数据和模型在一般科学界的广泛使用。 公共卫生相关性：许多目标与人类疾病直接相关。人类肠道中的共生细菌提供了巨大的代谢益处，但共生平衡的扰动与肥胖、癌症、炎症和其他疾病有关。对来自人类微生物组（肠道和其他）的蛋白质和其他生物医学上重要的PSI：生物学靶点的结构和生物学研究将为其功能提供宝贵的见解，并促进发现新的疾病治疗方法。

DESCRIPTION (provided by applicant): The Joint Center for Structural Genomics (JCSG) aims to participate in the NIGMS PSI:Biology program as a Center for High-Throughput Structure Determination. The JCSG high-throughput (HT) platform assembled over the past ten years will efficiently deliver large numbers of protein structures to the community by both x-ray crystallography and NMR on a wide range of targets from bacteria to human, including challenging targets such as eukaryotic proteins, protein-protein and other macromolecular complexes. Throughout PSI:Biology, the JCSG will adapt and tailor its operations to achieve the programmatic goals as they grow and evolve. The JCSG will continue to develop new technologies and methodologies, both experimental and computational, to address the spectrum of targets that will be presented, while keeping cost per structure to a minimum and quality to the highest standard. Integration within the PSI Network will be a high priority to embrace interactions with the Biology Partnership centers, future PARS, and the community, as well as support for all PSI Network activities, including the PSI-SGKB and PSI-MR. The JCSG will capitalize on its extensive experience to develop the best strategies to enhance chances of success and eliminate those that lead to failure. Contribution to the original PSI mission of extending structural coverage of the expanding protein universe will be advanced through judicious choice of targets, as will development of tools and collaborations that facilitate dissection of entire networks, pathways and molecular machineries for single organisms or cells from a structural perspective. The biomedical theme project will focus on the human microbiome. Interactions of commensal bacteria with the human body are profound and have a significant impact on maintenance of general human health, but are also associated with obesity, inflammatory diseases, diabetes and certain cancers to name but a few. The JCSG will leverage its HT platform to promote the biological and biomedical impact of all of its structures through extensive biophysical, functional and bioinformatics analyses in collaboration with the other PSI:Biology participants. Thus, the overall goal is to provide a robust, flexible HT structure determination platform that will meet the challenges and embrace the new opportunities that arise from the projects emanating from the PSI:Biology Partnerships and other PSI-supported projects. Furthermore, we will strive along with the PSI Network to promote widespread use of the PSI resources, materials, methodologies, data and models to the general scientific community. PUBLIC HEALTH RELEVANCE: Many of the targets have direct relevance to human disease. Commensal bacteria in the human gut provide tremendous metabolic benefits, but perturbation of the symbiotic balance is linked to obesity, cancer, and inflammatory and other diseases. Structural and biological studies of proteins from the human microbiome (gut and other) and other biomedically important PSI:Biology targets will provide invaluable insights into their function and enhance discovery of new therapeutics and treatments for disease.