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Molecular and Cellular Mechanisms of Wound Repair

伤口修复的分子和细胞机制

基本信息

批准号：
10657172
负责人：
SUSAN M PARKHURST
金额：
$ 46.56万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657172
关键词：
Accidents Actins Actomyosin Address Biochemical Biological Biological Assay Biological Process Cell Survival Cell membrane Cell model Cells Cessation of life Clinical Complement Complex Cytokinesis Cytoskeleton Development Discipline Disease Drosophila genus Drug Delivery Systems E-Cadherin Embryo Ensure Event Gene Family Genes Genetic Genetic Screening Goals Homeostasis Human Image Individual Infection Infection prevention Injury Integral Membrane Protein Ion Channel Lesion Malignant Neoplasms Mammalian Cell Medical Membrane Molecular Nature Neoplasm Metastasis Nuclear Envelope Organ Organism Pathway interactions Pattern Physiological Play Positioning Attribute Process Proteins Regenerative Medicine Regulation Research Role Rupture Speed Structure Time Tissues Trauma Work Wound models assault cell cortex cell injury clinically relevant daily functioning environmental stressor experience experimental study gene conservation genetic approach healing imaging approach improved injury and repair insight interest model organism novel therapeutics physiologic stressor preservation recruit repair model repaired response response to injury seal superresolution imaging wound wound closure wound healing

项目摘要

PROJECT SUMMARY/ABSTRACT Most cells of the body experience physiological and environmental stresses during their normal daily functions that can lead to a ruptured cell cortex (plasma membrane and underlying cortical cytoskeleton). The capacity of cells to rapidly repair general daily injuries, as well as ones resulting from trauma, infection, or diseases/cancer, is essential for their survival. The general aim of this proposal is to delineate how cells deal with such cell cortex disruptions to efficiently and effectively repair the lesions. We have developed a robust inducible single cell repair model using the syncytial Drosophila embryo that has superb amenability for live imaging and genetic tractability that is unavailable in other cell wound repair models. Our repair model has allowed us to successfully employ global genetic approaches for the first time to delineate the outline of cellular events and to identify many required genes/gene families providing clear molecular entry points for investigating specific key steps in the repair process. Our long-term goal is to establish the molecular framework underpinning cell wound repair. The specific aims of this proposal are 1) to determine the means by which the membrane plug re-seals the torn plasma membrane then facilitates wound closure; 2) to determine how the actin ring is attached to the overlying plasma membrane to coordinate their actions as the wound is pulled closed; and 3) to elucidate the basis of cell cortex remodeling following wound closure. Our findings will impact our understanding of cell wound repair across phyla, complement work done in other cell repair models, provide new insights into key players/events needed for efficient repair, as well as how they work in concert to achieve successful wound closure, and contribute to our understanding of related fundamental cellular and developmental events. Our studies are also expected to be of significant medical relevance, as understanding the molecules, machineries, and pathways governing cell wound repair will be extremely valuable for developing new or enhancing existing strategies for treating cellular damage, and for disciplines such as regenerative medicine where cell based constructs are used to reconstruct tissues or clinical drug delivery systems where molecules cross cell membranes.

项目总结/文摘

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prepatterning by RhoGEFs governs Rho GTPase spatiotemporal dynamics during wound repair.

DOI：
10.1083/jcb.201704145
发表时间：
2017-12-04
期刊：
The Journal of cell biology
影响因子：
0
作者：
Nakamura M;Verboon JM;Parkhurst SM
通讯作者：
Parkhurst SM

Rho family GTPase functions in Drosophila epithelial wound repair.

DOI：
10.4161/21541248.2014.982415
发表时间：
2015
期刊：
Small GTPases
影响因子：
0
作者：
Verboon JM;Parkhurst SM
通讯作者：
Parkhurst SM

Rho family GTPases bring a familiar ring to cell wound repair.

DOI：
10.4161/21541248.2014.992262
发表时间：
2015
期刊：
Small GTPases
影响因子：
0
作者：
Verboon JM;Parkhurst SM
通讯作者：
Parkhurst SM

Into the breach: how cells cope with wounds.

深入突破口：细胞如何应对伤口。

DOI：
10.1098/rsob.180135
发表时间：
2018
期刊：
Open biology
影响因子：
5.8
作者：
Nakamura,Mitsutoshi;Dominguez,AndrewNM;Decker,JacobR;Hull,AlexanderJ;Verboon,JeffreyM;Parkhurst,SusanM
通讯作者：
Parkhurst,SusanM

Coordination of Rho family GTPase activities to orchestrate cytoskeleton responses during cell wound repair.