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: 8656713
• 负责人: Wallace Marshall
• 金额: $ 22.37万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656713
• 关键词: Accounting; Affect; Behavior; Biological Models; Caliber; Cell Size; Cells; Cellular Structures; Cellular biology; Cereals; Chemicals; Chlamydomonas; Cilia; Complex; Cytoplasmic Protein; Data; Defect; Dill; Ensure; Equilibrium; Excision; Feedback; Flagella; Gene Mutation; Genes; Genetic; Genetic Transcription; Geometry; Goals; Green Algae; Growth; Hydrocephalus; Immobilized Cells; Injection of therapeutic agent; Length; Life; Link; Marshal; Measurement; Mediating; Methods; Microfluidics; Microscopy; Microtubules; Modeling; Molecular; Mutation; Organelles; Pathway interactions; Patients; Polycystic Kidney Diseases; Process; Protein Precursors; Regulation; Repressor Proteins; Series; Signal Transduction; Stochastic Processes; Structure; Subcellular structure; Symptoms; System; Systems Biology; Testing; Time; Time Series Analysis; Total Internal Reflection Fluorescent; Transcriptional Regulation; abstracting; base; cell type; fluid flow; gene induction; laser scissor; models and simulation; mutant; novel; particle; predictive modeling; public health relevance; statistics

DESCRIPTION (provided by applicant): Abstract The dynamics of complex intracellular structures pose many challenges for systems biology, one of which is to understand the control systems that regulate the size of cellular structures. The question of how cells control organelle size is currently an unanswered question in cell biology. We are focusing on the eukaryotic flagellum as a simplified, one-dimensional size control problem that facilitates quantitative measurement. We have constructed a coarse-grained model for length control in terms of turnover and transport of flagellar components. Preliminary data in which we quantitatively analyze intraflagellar transport and synthesis of flagellar components has caused us to re-evaluate the simple model. Basd on these preliminary results, we propose to develop a new integrated model for length control that will take into account a series of proposed quantitative measurements of transport and precursor synthesis in living cells, using the green alga Chlamydomonas as a model system. By combining dynamical systems modeling of the precusor synthesis pathway and stochastic modeling of intraflagellar transport, we will develop a model that can make novel predictions, particularly with respect to scaling and fluctuations. We will then perform model verification and parameter estimation using new experimental methods to probe scaling, fluctuation, and dynaimcs in the length control system in living cells. We will leverage the genetic power of Chlamydomonas by repeating measurements and model regression in mutants in defined genes that alter length, allowing us to link model parameters with molecular pathways and components. We expect, by completing our aims, to have one of the first fully predictive models for a cellular size control system, which we hope will serve as a paradigm for systems-level analysis of cellular structural dynamics.

描述（由申请人提供）：