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Analysis of Early Mouse Cerebellar Neuron Developmental Control Pathways

早期小鼠小脑神经元发育控制通路分析

基本信息

批准号：
7253127
负责人：
WILLIAM J BOSL
金额：
$ 20.17万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7253127
关键词：
Adopted Biochemical Biochemical Pathway Candidate Disease Gene Cell Cycle Progression Cell Cycle Regulation Cell Surface Proteins Cells Characteristics Complex Computer Simulation Computing Methodologies Condition Cytokinesis Data Data Sources Databases Defect Detection Development Disease Drug Delivery Systems Elements Epigenetic Process Eukaryota Eukaryotic Cell Evolution Exhibits Financial compensation Fuzzy Logic Gene Deletion Gene Expression Gene Proteins Generations Genes Genetic Genetic Crosses Genome Genomics Goals Growth High temperature of physical object Immune system Knock-out Lead Life Literature Malignant Neoplasms Measurement Measures Medical Medicine Methods Microarray Analysis Mitosis Mitotic Modeling Modification Molecular Profiling Mus Mutation Neurons Organism Paper Pathway interactions Pattern Pharmaceutical Preparations Play Protein Databases Protein Overexpression Publications Publishing Regulation Role Saccharomycetales Signal Pathway Source Spectrum Analysis Structure System Systems Biology Techniques Testing Therapeutic Time base cancer cell cellular imaging cold temperature deletion analysis design disorder control epigenetic variation gene interaction insight mutant pathogen practical application programs research study response simulation therapy development

项目摘要

DESCRIPTION (provided by applicant): The ability of cells and organisms to generate heritable alternative strategies through genetic or epigenetic variations is not well understood and is a central issue in evolution and disease control. The contribution of network complexity to evolvability of new cellular mechanisms is directly relevant to a variety of medical concerns. For example, cancer cells have incredible abilities to escape treatments that are intended to block their growth. Pathogens are known to use epigenetic and genetic modifications to rapidly switch expression of cell-surface proteins to escape detection by the immune system. An important task for quantitative genomic medicine is to characterize the adaptive response of cells to perturbations by drugs or mutation, then to quantify them with models and predict the patterns of adaptation. A systems approach will be adopted to characterize the complex genetic or epigenetic changes in budding yeast cells in response to perturbations of the mitotic exit network. The mitotic exit network (MEN) is a complicated regulatory network that interacts with several other important pathways to control the timing of mitotic exit and cytokinesis. The fundamental goal is to determine if characteristic patterns and organizational principles are exhibited in suppressors when key genes are deleted from the MEN pathway. Genetic crosses, live cell imaging, and microarray expression measurements will be used to characterize adaptations. Then data from recent publications will be integrated with corroborating data from several sources to build computational models of the MEN and adaptations, which will be analyzed and compared quantitatively to discover patterns. This may provide insights into how network complexity contributes to the activation of new cellular mechanisms and may have practical applications for predicting the possible response of cells to targeted drug treatments.

描述（由申请人提供）：细胞和生物体通过遗传或表观遗传变异产生可遗传替代策略的能力尚未得到充分理解，并且是进化和疾病控制中的中心问题。网络复杂性对新细胞机制进化的贡献与各种医学问题直接相关。例如，癌细胞具有令人难以置信的能力来逃避旨在阻止其生长的治疗。众所周知，病原体利用表观遗传和遗传修饰来快速改变细胞表面蛋白的表达，以逃避免疫系统的检测。定量基因组医学的一项重要任务是表征细胞对药物或突变扰动的适应性反应，然后用模型对其进行量化并预测适应模式。将采用系统方法来表征出芽酵母细胞响应有丝分裂出口网络的扰动而发生的复杂遗传或表观遗传变化。有丝分裂退出网络 (MEN) 是一个复杂的调节网络，它与其他几个重要途径相互作用，以控制有丝分裂退出和胞质分裂的时间。基本目标是确定当关键基因从 MEN 通路中删除时，抑制基因是否表现出特征模式和组织原则。遗传杂交、活细胞成像和微阵列表达测量将用于表征适应性。然后，来自最近出版物的数据将与来自多个来源的确凿数据相整合，以构建 MEN 和适应的计算模型，并对这些模型进行定量分析和比较以发现模式。这可能有助于了解网络复杂性如何促进新细胞机制的激活，并且可能具有预测细胞对靶向药物治疗的可能反应的实际应用。