PLATELET TOMOGRAPHY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。血小板是由巨噬细胞产生的小（3微米直径和<1微米厚）细胞碎片。它们在血流中循环，并在初级止血中发挥重要作用。一些血小板缺陷可导致一系列出血性疾病，而另一些血小板缺陷可显著增加血栓形成事件（如肺栓塞、心脏病发作和中风）的风险。血小板天然缺乏细胞核，使它们比典型的真核细胞薄得多，但它们仍然含有线粒体，微管，肌动蛋白细胞骨架和其他真核细胞特征。它们还包含其作用所特有的其他结构。因此，它们是通过电子冷冻断层扫描进行结构分析的极好目标。 我们的目标是：1）以3D方式描述血小板的细胞结构;细胞骨架，包括肌动蛋白和微管;膜系统，包括血浆和细胞内;其他细胞器，如线粒体;和大分子机器，如核糖体等;最后是他们之间的关系。2)所有这些结构和关系在凝血信号激活后发生变化。我们可以通过建立一个激活的时间过程来观察事件的进展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Blood platelets are small (3 micron diameter and <1 micron thick) cellular fragments generated from macrophages. They circulate in the bloodstream and play a major role in primary hemostasis. Some platelet defects can lead to an array of bleeding disorders, while others can significantly increase risk for thrombotic events such as pulmonary embolism, heart attack and stroke. Platelets naturally lack nuclei, rendering them much thinner than typical eukaryotic cells, yet they still contain mitochondria, microtubules, an actin cytoskeleton and other eukaryotic features. They also contain other structures unique to their role. Thus they are an excellent target for structural analysis by electron cryotomography. Our goals are 1) to describe the cellular structures of platelets in 3D; the cytoskeleton, including actin and microtubules; the membrane systems, both plasma and intracellular; other organelles such as mitochondria; and macromolecular machines such as ribosomes, etc.; and finally their relationships to each other. 2) All these structures and relationships change upon activation by a clotting signal. We can observe the progression of events by setting up a time course of activation.