Spinning Disk Confocal Microscope System

描述(由申请人提供)：威斯康星州血液中心血液研究所(BRI)对血液相关研究有既定的、长期的承诺。目前，19名首席研究员领导心血管生物学、免疫学、干细胞生物学、输血医学、出血和血栓控制等领域的研究项目。该研究所在血小板和血管细胞生物学方面具有较强的研究实力，并将其研究成果应用于出血性疾病、血液疾病、心脏病发作和中风的治疗。许多一带一路研究人员的研究项目已经进入了涉及各种人类疾病动物模型的研究。在体内进行的实验需要专门的工具来获得生理相关条件下的数据。我们申请资金购买旋转盘共聚焦显微镜系统，用于活体成像，以实现本申请中主要和次要用户所描述的研究目标。由美国国立卫生研究院资助的12名研究人员发起的项目和由两名新研究人员发起的项目需要这一工具来实现他们的研究目标。这些项目的题目是：PECAM-1的分子生物学和功能；血小板激活和黏附的分子机制；FVIII和VWF的生物分子相互作用；VWF对VWD的分子影响；VWD诊断中的比较有效性；哮喘增加镰状细胞疾病的血管闭塞；镰状细胞疼痛的伤害机制；血小板活性的负调节；VWF在体外/体内变化的分子机制；肝素诱导的血小板减少中B细胞的反应；CD36在血栓形成中调节抗血管生成开关；CD36信号在血栓形成中的机制作用；TFPI与内皮的关系；血小板TFPI激活的生化和生理学；用于放射联合损伤治疗的C；活化蛋白C在脓毒症治疗中的作用机制；血友病A的血小板衍生FVIII基因治疗；kindlin-2在B3整合素激活中的作用机制；血小板功能在血友病相关性胎盘血管疾病中的作用。旋转圆盘共聚焦显微镜系统将成为BRI新成立的血栓核心实验室的一部分，并将使科学家能够在活体动物模型中评估影响血流和血栓形成的各种实验参数。

DESCRIPTION (provided by applicant): The Blood Research Institute (BRI) of BloodCenter of Wisconsin has an established, long-term commitment to blood-related research. Currently 19 Principal Investigators lead research programs in the fields of cardiovascular biology, immunology, stem cell biology, transfusion medicine, control of bleeding and thrombosis. The BRI has had a tradition of research strength in platelet and vascular cell biology and have applied their research findings to the treatment of bleeding disorders, blood diseases, heart attack and stroke. The research programs of many BRI investigators have moved into studies involving various animal models of human disease. Experiments performed in vivo require specialized tools to obtain data under physiological relevant conditions. We request funds to purchase a spinning disk confocal microscope system for intravital imaging to accomplish the research goals described by the major and minor users in this application. Projects initiated by twelve NIH-funded Investigators and those initiated by two new investigators require this instrument to accomplish their research goals. These project titles are: Molecular biology and function of PECAM-1; Molecular mechanisms of platelet activation and adhesion; Biomolecular interactions of FVIII and VWF; Molecular impact of VWF on VWD; Comparative effectiveness in the diagnosis of VWD; Asthma increases vaso-occlusion in sickle cell disease; Nociceptive mechanism underlying sickle cell pain; Negative regulation of platelet activity; Molecular mechanisms of VWF alteration in vitro/vivo; B-cell responses in heparin induced thrombocytopenia; Regulation of the anti- antiangiogenic switch by CD36 in thrombosis; Mechanistic role of CD36 signaling in thrombosis; Association of TFPI with endothelium; The biochemistry and physiology of platelet TFPI; Activated Protein C for Treatment of Radiation Combined Injury; Mechanism of Activated Protein C Action in Sepsis Therapy; Platelet- derived FVIII gene therapy of hemophilia A; Mechanism of kindlin-2 in B3 integrin activation; Platelet Function in Thrombophilia-Associated Placental Vascular Disorder. The spinning disk confocal microscope system will become a part of the newly formed Thrombosis Core Lab at the BRI and will enable scientists to evaluate various experimental parameters that affect blood flow and thrombus formation in live animal models.