Modeling and Analysis of the Flagellar Length Control System

鞭毛长度控制系统的建模与分析

• 批准号: 8912834
• 负责人: Wallace Marshall
• 金额: $ 30.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912834
• 关键词: Address; Affect; Animal Model; Attention; Back; Biological Models; Carrier Proteins; Cells; Cellular biology; Chemicals; Chlamydomonas; Cilia; Computer Simulation; Coupled; Cytoplasmic Protein; Data; Data Analyses; Data Set; Defect; Diffuse; Diffusion; Disease; Ensure; Equilibrium; Feedback; Flagella; Genes; Genetic; Geometry; Hydrocephalus; Image; Image Analysis; Individual; Injection of therapeutic agent; Kinesin; Lead; Length; Life; Marshal; Measurement; Measures; Methods; Microtubules; Modeling; Molecular; Mutation; Non-linear Models; Organelles; Patients; Performance; Photobleaching; Polycystic Kidney Diseases; Regulation; Role; Shapes; Signal Transduction; Speed; Structure; Symptoms; System; Testing; Time; Time Series Analysis; Work; base; cell motility; cellular imaging; fluid flow; genetic manipulation; kinetosome; particle; public health relevance; quantitative imaging; research study

 DESCRIPTION: The means by which cells regulate the size of their organelles is a fundamental unanswered question in cell biology. Cilia and flagella provide a convenient model system to study the general question of organelle size control due to their simple one- dimensional shape. Assembly of cilia and flagella requires a kinesin based motility called intraflagellar transport (IFT), and this transport is also required to maintain ciliary length afte assembly. The central role of IFT in ciliary assembly, combined with the fact that perturbations in IFT can lead to cilia-related diseases, has focused attention on the mechanisms that regulate IFT activity. We have used quantitative live cell image analysis to show that IFT particles are injected into the flagellum at a rate that depends on the flagellar length, suggesting some regulatory linkage between flagellar length and IFT injection, but the mechanism of this regulation is not understood. This proposal will test specific models for how length may regulate IFT using a combination of quantitative live cell image analysis and experimental perturbations, coupled with modeling and nonlinear time series analysis methods. We will also integrate IFT regulation with regulation of disassembly and of precursor synthesis into a combined control system model based on three separate feedback loops, and use experimental perturbations to test the contributions that individual feedback loops make to overall system performance. Our work combines quantitative live cell imaging and computational modeling with the powerful genetics of the unicellular model organism Chlamydomonas for probing flagellar dynamics.