Chemical Genetic Screens for Mitochondrial Division and Fusion Inhibitors

描述（由申请人提供）：我们建议在分子库筛选中心网络中进行高通量筛选，该筛选与在较小筛选规模上已经成功鉴定线粒体裂变和融合抑制剂的筛选相同。具体而言，我们将采用简单的生长为基础的测定在S。酿酒酵母菌株监测线粒体分裂和融合活性以鉴定另外的小分子抑制剂。鉴于我们的成功，我们有信心将发现许多新的化合物，线粒体膜动力学调控的事件，如细胞凋亡的医学重要性，表明化学遗传方法也可能导致识别和开发新的治疗药物中风，心肌梗死，神经退行性疾病和癌症。我们相信，这些化合物的新的治疗潜力，我们在寻找其靶点方面的专业知识，以及我们利用它们更充分地了解机制的独特能力，证明了我们在此资助机制下扩大筛选的要求是合理的。我们建议在分子库筛选中心网络中进行高通量筛选，与在较小筛选规模上已经成功鉴定线粒体裂变和融合抑制剂的筛选中心网络相同。具体而言，我们将采用简单的生长为基础的测定在S。酿酒酵母菌株监测线粒体分裂和融合活性以鉴定另外的小分子抑制剂。鉴于我们的成功，我们有信心将发现许多新的化合物。线粒体膜动力学调控的事件（如细胞凋亡）的医学重要性表明，化学遗传学方法也可能导致识别和开发新的治疗药物，用于中风，心肌梗死，神经退行性疾病和癌症。我们相信，这些化合物的新的治疗潜力，我们在寻找其靶点方面的专业知识，以及我们利用它们更充分地了解机制的独特能力，证明了我们在此资助机制下扩大筛选的要求是合理的。

DESCRIPTION (provided by applicant): We propose to conduct a high through put screen in the Molecular Libraries Screening Centers Network identical to the one that, on a smaller screening scale, has already successfully identified mitochondrial fission and fusion inhibitors. Specifically, we will employ straightforward growth-based assays in S. cerevisiae strains that monitor mitochondrial fission and fusion activity to identify additional small molecule inhibitors. Given our success, we are confident that many novel compounds that will be found. The medical importance of events regulated by mitochondrial membrane dynamics, such as apoptosis, indicates that the chemical genetic approach may also lead to the identification and development of novel therapeutic agents for stroke, myocardial infarction, neurodegenerative diseases, and cancer. We believe that the novel therapeutic potential of these compounds, our expertise in finding their targets, and our unique ability to exploit them to more fully understand mechanism, justifies our request to expand our screen under this funding mechanism. We propose to conduct a high through put screen in the Molecular Libraries Screening Centers Network identical to the one that, on a smaller screening scale, has already successfully identified mitochondrial fission and fusion inhibitors. Specifically, we will employ straightforward growth-based assays in S. cerevisiae strains that monitor mitochondrial fission and fusion activity to identify additional small molecule inhibitors. Given our success, we are confident that many novel compounds will be found. The medical importance of events regulated by mitochondrial membrane dynamics, such as apoptosis, indicates that the chemical genetic approach may also lead to the identification and development of novel therapeutic agents for stroke, myocardial infarction, neurodegenerative diseases, and cancer. We believe that the novel therapeutic potential of these compounds, our expertise in finding their targets, and our unique ability to exploit them to more fully understand mechanism, justifies our request to expand our screen under this funding mechanism.