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Understanding developmental control of cell polarity using single-cell in vivo biochemistry

使用单细胞体内生物化学了解细胞极性的发育控制

基本信息

批准号：
10225558
负责人：
Daniel J Dickinson
金额：
$ 37.18万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10225558
关键词：
Age Animals Anterior Apical Biochemical Biochemistry Biological Models Biological Process Caenorhabditis elegans Cell Cycle Cell Polarity Cell Separation Cells Characteristics Complex Cues Data Defect Development Disease Disseminated Malignant Neoplasm Embryo Eukaryotic Cell Foundations Genetic Goals Homeostasis In Vitro Individual Knowledge Learning Link Malignant Neoplasms Maps Measurement Membrane Methods Microscopy Mission Molecular Mutagenesis National Institute of General Medical Sciences Outcome Phosphotransferases Play Positioning Attribute Prevention Protein Kinase Proteins Regulation Research Role Signal Pathway Signal Transduction Somatic Cell Specific qualifier value Stereotyping System Testing Tissues Work age related base cell behavior cell type disease diagnosis experimental study extracellular in vivo in vivo Model innovation novel polarized cell prevent programs protein complex protein protein interaction response single molecule sperm cell tool zygote

项目摘要

Project Summary / Abstract Cell polarity is a fundamental feature of eukaryotic cells, and must be coordinated between cells and regulated to allow for normal animal development and tissue homeostasis. Despite genetic identification of proteins involved in cell polarity and a large body of knowledge about their interactions in vitro, it remains unclear how polarity proteins are organized into signaling complexes in cells. This lack of knowledge has prevented the field from understanding mechanisms of developmental control of polarity signaling in vivo. The long-term goal of the proposed research is to resolve the network of protein-protein interactions that supports animal cell polarity and to understand how this network can respond to developmental signals. To enable progress towards this goal, the applicants have developed innovative experimental tools that allow single-molecule measurements of native protein complex abundance in single cells. This project focuses on two evolutionarily conserved protein kinases, called aPKC and PAR-1, that play central roles in polarity by localizing to opposite ends of a polarized cell and dictating polarized cell behaviors. The applicants will make use of the C. elegans early embryo, in which cells reproducibly polarize in response to multiple spatial and temporal cues, to discover mechanistic links between developmental signals and the polarity machinery. The central hypothesis of this work is that that developmental signals control cell polarity by altering the molecular complexes in which aPKC and PAR-1 reside. This hypothesis will be explored by identifying dynamic aPKC and PAR-1 complexes that control polarity (Aim 1); by determining how polarity signaling is coordinated with cell cycle cues in the zygote (Aim 2); and by determining how developmental cues re-program polarity signaling in later embryos. The work proposed in this application is significant because it will reveal fundamental mechanisms controlling cell polarity, and because it places these mechanistic studies in a developmental context. The proposed work is innovative, in the applicant’s opinion, because it uses novel experimental methods to perform biochemical, mechanistic studies in vivo. By studying the biochemical control of aPKC and PAR-1 in multiple cellular and developmental contexts in a single experimental system, this work will identify fundamental mechanisms of PAR polarity signaling and to learn how these mechanisms are deployed to achieve different outcomes during development.

项目摘要/摘要