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Image-derived Spatiotemporal Models of Cellular Organization and Perturbation

细胞组织和扰动的图像衍生时空模型

基本信息

批准号：
9042386
负责人：
Robert F Murphy
金额：
$ 31.39万
依托单位：
CARNEGIE-MELLON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9042386
关键词：
Accounting Affect Alleles Behavior Biochemical Reaction Biochemistry Biological Assay Cell Cycle Cell Shape Cell model Cell physiology Cells Cellular Structures Complex Computer software Computing Methodologies Cytopathology Data Defect Dependence Dependency Disease Dysplasia Endoplasmic Reticulum Fluorescence Microscopy Foundations Future Genes Golgi Apparatus Grant Health Health Sciences Hematological Disease Hereditary Spastic Paraplegia Heterogeneity Image Lead Learning Length Life Maintenance Measures Methods Microscopy Modeling Molecular Molecular Biology Morphology Mutation Nuclear Organelles Organizational Change Pathway interactions Pattern Pharmaceutical Preparations Phenotype Play Population Positioning Attribute Preclinical Drug Evaluation Process Proteins RNA interference screen Research Reticular Cell Role Shapes Statistical Models Structure Subcellular structure System Testing Therapeutic Time Tissues Toxic effect Visual base computer framework computerized tools environmental change fluorescence imaging genetic variant instrumentation learning strategy microscopic imaging model development movie mutant open source response screening spatiotemporal temporal measurement tool

项目摘要

DESCRIPTION (provided by applicant): This research is aimed at developing and testing methods that will enable automated, information--‐rich studies of the subcellular organization of proteins and other biomolecules. We propose to develop the computational foundation for deciphering the spatiotemporal morphological pathways of different subcellular structures during important subcellular processes automatically from microscopy images. We will leverage our progress in the previous project period, in which we established the Cell Organizer system for building image-‐derived models of cell organization, to build new modeling capabilities for cisternal and reticular structures, for capturing the relationships between different cellular components, and for learning how aspects of cell organization change during processes such as the cell cycle. Given the importance of the endoplasmic reticulum in numerous cellular processes (as well as diseases including hematological disorders, cranio--‐ lenticulo--‐sutural dysplasia, chylomicro retention disease, etc.), we expect the modeling approaches we propose to provide important mechanistic clues as to the "normal" (non-- athological) morphological pathways of these structures and how they may be perturbed in disease. To provide valuable images to drive the development of modeling capabilities, and to simultaneously identify candidate lead compounds for treatment of diseases with ER defects, we will conduct extensive compound screening studies on cells expressing normal and mutant alleles of atlastin (which plays a critical role in ER structure). The computational methods we develop will be integrated into our open source CellOrganizer system (http://CellOrganizer.org). In addition to the applications mentioned above, we anticipate the computational frameworks we develop will be valuable for a wide range of imaging assays including drug screens, RNAi screens, cytology, and pathology.