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Molecular, cellular, and developmental mechanisms of septin disease alleles

脓毒症等位基因的分子、细胞和发育机制

基本信息

批准号：
10389578
负责人：
Jenna Ann Perry
金额：
$ 6.76万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10389578
关键词：
Abnormal Cell Affect Alleles Animals Architecture Behavior Biophysics Caenorhabditis elegans Cancerous Cell Maintenance Cell Polarity Cell Shape Cell membrane Cell physiology Cells Cellular biology Clinical Communities Cytokinesis Cytoskeletal Modeling Cytoskeletal Proteins Cytoskeleton Defect Deposition Development Developmental Biology Disease Disease Progression Embryo Embryonic Development Epithelial Family Fellowship Fibrosis Filament Fluorescence Microscopy Functional disorder Gene Family Genes Goals Higher Order Chromatin Structure Human In Situ In Vitro Infertility Knowledge Lead Life Malignant Neoplasms Mammals Mechanics Membrane Microscopy Missense Mutation Modeling Molecular Molecular Biology Molecular and Cellular Biology Motor Mutate Mutation Nematoda Neuropathy Organism Pathology Platelet aggregation Play Polymers Protein Isoforms Proteins RNA Splicing Research Resolution Resources Role Rotation Scaffolding Protein Shapes Structure System T-Lymphocyte Tissues Training Universities Work cell type combinatorial diagnostic tool disease diagnostic experimental study gene product genome editing high resolution imaging human disease in vivo insight intermolecular interaction migration novel diagnostics novel therapeutic intervention polymerization professor programs protein function reconstitution reproductive scaffold skills stem therapeutic target tissue-level behavior trafficking tumor

项目摘要

PROJECT SUMMARY/ABSTRACT Cell function and tissue integrity rely on the maintenance of cell shape and organization. The cytoskeleton, containing polymers and motor proteins, serves to structure and remodel the cell in addition to facilitating tissue architecture. A conserved filament-forming family, the septins, influences the cytoskeleton by serving as a protein scaffold and septin dysregulation may promote many human diseases. The goal of this proposal is to understand how septins contribute to cell and tissue behavior and organization through the use of septin alleles found in human disease. I will combine high-resolution imaging, cell biology, molecular biology, developmental biology, genome editing, and biophysics to achieve the forestated goal. My work will be directed by three aims: (1) Investigate how clinical septin mutations and depletion affect tissue organization and function; (2) Elucidate how septin mutations perturb cytokinesis; (3) Define how septin mutation affects polymerization and higher-order structure function. The proposed experiments will establish the use of C. elegans as an in vivo system to overcome current limitations surrounding septin study and will provide insight into how septin dysfunction can perturb cell and tissue organization and function during human disease.

项目总结/文摘