Model Organisms

模式生物

基本信息

批准号：
8899501
负责人：
JEFFREY L. BRODSKY
金额：
$ 18.48万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8899501
关键词：
Affect Animal Model Area Autophagocytosis BK Virus Biochemical Biogenesis Biological Assay Biological Models Cell Death Cell physiology Chemicals Clinical Sciences Collaborations Complement Complex Cystic Fibrosis Data Development Developmental Biology Disease Embryo Ensure Epithelial Cells Funding Genetic Genetic Screening Genomics Goals Homeostasis Human Resources Injury Institutes Instruction International Kidney Kidney Diseases Knowledge Lead Link Methods Mission Modeling Molecular Chaperones Morphology Organism Organogenesis Paper Pathway interactions Preclinical Testing Proteins Proteomics Publications Reporter Research Research Personnel Saccharomyces cerevisiae Services Signal Transduction System Technology Testing Time Transgenic Organisms Translating Translational Research Ubiquitin Universities Work Yeasts Zebrafish base cell type combinatorial chemistry drug discovery in vivo kidney cell meetings multicatalytic endopeptidase complex nephrogenesis prevent progenitor protein function protein structure function protein transport research study reverse genetics screening secretory protein small molecule tool trafficking

项目摘要

PROJECT SUMMARY (See instructions): The Model Organisms Core will employ two genetically-tractable systems, the yeast S. cerevisiae and the zebrafish D. rerio, each with distinct advantages. These experimental systems will help dissect fundamental aspects of kidney development and protein structure and function. Experiments associated with these model systems will be complemented by the use of small molecule modulators that have emerged from Core associated activities over the past four years. Hypotheses arising from the unique attributes of the yeast and zebrafish models and from the use of chemical modulators will continue to be tested in higher cell types and organisms via the other Cores. In turn, experiments using yeast and zebrafish provide rapid assessments of predictions from more complex systems. The goals of the Yeast Core are to develop and continue to utilize established expression systems for wild type and disease-causing proteins that transit the secretory pathway in kidney cells. Genomic and proteomic attacks will identify factors that impact their biogenesis, and the mechanism of action of these factors will be established. Toward these goals, the Yeast Core has created over a dozen expression systems and offers collaborators the expertise and tools to co-opt this model organism. Specific assays developed in the Core include methods to assess how chaperones, the ubiquitin proteasome pathway, autophagy, and chemical chaperones impact secretory protein biogenesis. The Zebrafish Core will utilize established transgenic kidney reporter lines and to utilize established automated screening technologies in small molecule screens to identify chemical probes for kidney development and disease. The Zebrafish Core has a number of transgenic lines and identified small molecules that impact kidney development, and has pinpointed when specific factors act during kidney development. Collaborators will be able to establish and analyze results from newly created zebrafish lines and perform small molecule screens. Overall, the knowledge gained from the use of these complementary model organisms will be expanded via collaborations with the other Cores, and in turn the hypotheses that arise from more complex systems can be rapidly and in some cases more thoroughly tested in yeast and zebrafish. The Core will co-

项目摘要（请参阅说明）：模型生物体核心将采用两个可摘要的系统，即酵母菌酿酒酵母和斑马鱼D. Rerio，每种都有明显的优势。这些实验系统将有助于剖析肾脏发育以及蛋白质结构和功能的基本方面。与这些模型系统相关的实验将通过在过去四年中从核心相关活性中出现的小分子调节剂的使用来补充。由酵母和斑马鱼模型的独特属性以及使用化学调节剂的使用引起的假设将继续通过其他核心在较高的细胞类型和生物中进行测试。反过来，使用酵母和斑马鱼的实验提供了对更复杂系统的预测的快速评估。酵母核心的目标是开发并继续利用已建立的表达系统，用于传播肾细胞分泌途径的野生型和引起疾病的蛋白质。基因组和蛋白质组学攻击将确定影响其生物发生的因素，并将确定这些因素的作用机理。为了实现这些目标，酵母核心已经建立了十几个表达系统，并为合作者提供了选择这种模型有机体的专业知识和工具。核心中开发的特定测定法包括评估伴侣，泛素蛋白酶体途径，自噬和化学伴侣如何影响分泌蛋白质生物发生的方法。斑马鱼核心将利用已建立的转基因肾脏记者线，并利用小分子筛选中已建立的自动筛选技术来鉴定肾脏发育和疾病的化学探针。斑马鱼核具有许多转基因线，并鉴定出影响肾脏发育的小分子，并且在肾脏发育过程中的特定因素作用时已指出。合作者将能够建立和分析新创建的斑马鱼线的结果并执行小分子屏幕。总体而言，从使用这些互补模型生物的使用中获得的知识将通过与其他核心的合作进行扩展，进而可以迅速在酵母和斑马鱼中更彻底地测试的假设。核心将共同