Project 2

NYSGRC在高吞吐量结构确定以及 发现和实施基础设施，以提高速度、准确性、成功率和经济性 结构生物学研究。展望未来，NYSGRC将进行重组，以满足新的和多样化的需求。 与PSI相关的挑战：生物学网络。除了依赖传统的高通量 细菌表达平台，NYSGRC将开发和实施尖端的实验和 计算技术来检查生物学上重要的分子， PshBiology.这些靶标可能包括多结构域真核蛋白、多组分蛋白、多功能蛋白、多功能蛋白和多功能蛋白。 组装和分泌的蛋白质，这些蛋白质是复杂的多细胞生物学的基础，并直接有助于 人类健康和疾病。除了为高通量结构生物学服务外， 合作伙伴关系，这一基础设施将支持我们的生物主题，重点是分泌机制 和来自主要细菌、原生动物和真菌病原体的分泌效应蛋白。这些目标是 特别选择，以提供新的见解，这些病原体已经演变为 免疫逃避和调节宿主信号传导途径。这些过程依赖于复杂的纳米机器， 与细胞质，膜相关和细胞外成分，这需要杂交 计算和实验方法来定义它们的组织，结构和功能。最后我们 综合的实验和计算工作已经确定了新的机会， 经济地增强序列/结构覆盖。 PShBiology的出现正在推动NYSGRC的进化变革过程， 增强了其出色的高通量结构测定管线。我们的实力在传统 细菌表达，再加上新的方法，真核表达和重折叠，以及我们的 在混合方法方面的专业知识，使我们能够独特地支持PShBiology的努力。

The NYSGRC has a 10-year proven track record in high-throughput structure determination as well as in discovering and innplementing infrastructure to increase the speed, accuracy, success rate and affordability of structural biology studies. Moving forward the NYSGRC will reorganize to meet the new and diverse challenges associated with the PSI:Biology Network. In addition to reliance on traditional high-throughput bacterial expression platforms, the NYSGRC will develop and implement cutting-edge experimental and computational technologies to examine the biologically important molecules that are the focus of PShBiology. These targets are likely to include multidomain eukaryotic proteins, multi-component assemblies, and secreted proteins that underly complex multi-cellular biology and directly contribute to human health and disease. In addition to servicing the High-Throughput-Enabled Structural Biology Partnerships, this infrastructure will support our Biological Theme that focuses on the secretion machinery and secreted effector proteins from major bacterial, protozoan and fungal pathogens. These targets were specifically selected to provide new insights into the mechanisms that these pathogens have evolved for immune evasion and modulation of host signaling pathways. These processes rely on intricate nanomachines, with cytoplasmic, membrane-associated and extracellular components, that require hybrid computational and experimental approaches to define their organization, structure and function. Finally, our integrated experimental and computational efforts have identified new opportunities to significantly and economically enhance sequence/structure coverage. The advent of PShBiology is driving a process of evolutionary change for the NYSGRC that has already enhanced its outstanding high-throughput structure determination pipeline. Our stengths in traditional bacterial expression, coupled with novel approaches to eukaryotic expression and refolding, as well as our established expertise in hybrid methods, postions us to uniquely support the efforts of PShBiology.