The NYSGRC: A Large Scale Center for PSI:Biology

NYSGRC在高通量结构确定以及发现和实施基础设施方面拥有10年的良好记录，以提高结构生物学研究的速度、准确性、成功率和可负担性。展望未来，NYSGRC将进行重组，以迎接与PSI：生物学网络相关的新的多样化挑战。除了依赖传统的高通量细菌表达平台外，NYSGRC还将开发和实施尖端的实验和计算技术，以检查PSI：生物学重点的生物学重要分子。这些靶标可能包括多结构域真核蛋白、多组分组装体以及构成复杂多细胞生物学基础并直接影响人类健康和疾病的分泌蛋白。除了为高通量结构生物学合作伙伴关系提供服务外，该基础设施还将支持我们的生物学主题，重点关注主要细菌，原生动物和真菌病原体的分泌机制和分泌效应蛋白。这些靶点是专门选择的，以提供新的见解，这些病原体已经进化为免疫逃避和宿主信号通路的调节机制。这些过程依赖于复杂的纳米机器，包括细胞质、膜相关和细胞外成分，需要混合计算和实验方法来定义它们的组织、结构和功能。最后，我们的综合实验和计算工作已经确定了新的机会，以显着和经济地提高序列/结构覆盖。

The NYSGRC has a 10-year proven track record in high-throughput structure determination as well as in discovering and implementing 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 PSI:Biology. These targets are likely to include multidomain eukaryotic proteins, multi-component assemblies, and secreted proteins that underlay 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 nano-machines, 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 PSI:Biology is driving a process of evolutionary change for the NYSGRC that has already enhanced its outstanding high-throughput structure determination pipeline. Our strengths in traditional bacterial expression, coupled with novel approaches to eukaryotic expression and refolding, as well as our established expertise in hybrid methods, positions us to uniquely support the efforts of PSI:Biology.