PECASE: Adhesion and Mechanics of Normal and Dystrophic Muscle Cells - A Cellular Engineering Basis for Gene Therapy
PECASE:正常和营养不良的肌肉细胞的粘附和力学 - 基因治疗的细胞工程基础
基本信息
- 批准号:9876328
- 负责人:
- 金额:$ 26.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-07-01 至 2006-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
9876328DischerTo achieve tissue integrity and resilience, cells must have sufficient ability to adhere and deform with tissue structures or matrices. One overall goal of this NSF-CAREER proposal is to develop novel approaches to cell adhesion, with a particular focus on muscular dystrophy (MD). A second goal is to create new educational opportunities and resources in the broader, emerging area of cell and molecular engineering. Integration of these research and education plans is expected to promote partnerships for the transfer of engineering research to both the clinical and industrial sectors, to prepare an increased number of underrepresented minorities and women for achievement in engineering science, and to expose a broad-based audience to the excitement of discovery.Motivation for detailed study of muscle cell adhesion is provided by burgeoning treatments of gene therapy for MD, a collection of common, debilitating, and often fatal genetic disorders. Though adhesion and cytoskeletal proteins at the cell membrane are loosely implicated in these disorders, very little is known in terms of quantitative aspects of function. Novel, patterned protein substrates -- of potential interest to industry and tissue engineers -- will first be engineered to geometrically control the growth and differentiation of muscle cells. Individual cells grown on these defined substrates will then be forcibly peeled from the substrates. Various optical microscopies will allow quantitative analysis at the nano- to micro- scales. The responses of several dystrophic-type muscle cells will be compared to normal cells with the intent of complementing and motivating gene therapy efforts which are emerging. Theoretical models at multiple scales, including an inextensible tape-peeling model and "molecular" element models rooted in molecular mechanics, will be pursued to advance structure-function hypotheses on cell membrane mechanics and adhesion.A complementary educational plan in the broader area of cell and molecular engineering is proposed for various academic levels as well as for the general public. An in-lab internship program will enable the mentoring of undergraduates from diverse backgrounds. New hands-on cell and molecular engineering laboratory exercises for diverse audiences will supplement focused course offerings at undergraduate and graduate levels of the engineering curriculum, and a public-access internet site will be dedicated to Education in Cell and Molecular Engineering (http://www.seas.upenn.edu/ ~discher/ cme.html).
9876328Discher为了实现组织完整性和弹性,细胞必须具有足够的能力与组织结构或基质粘附和变形。 这项 NSF-CAREER 提案的总体目标之一是开发细胞粘附的新方法,特别关注肌营养不良症 (MD)。 第二个目标是在更广泛的新兴细胞和分子工程领域创造新的教育机会和资源。 这些研究和教育计划的整合预计将促进合作伙伴关系,将工程研究转移到临床和工业部门,为更多代表性不足的少数族裔和女性在工程科学方面取得成就做好准备,并使广大受众接触到发现的兴奋。对肌肉细胞粘附的详细研究是由新兴的MD基因治疗方法提供的,MD是一系列常见的、 使人衰弱且常常致命的遗传性疾病。 尽管细胞膜上的粘附蛋白和细胞骨架蛋白与这些疾病有松散的关联,但在功能的定量方面却知之甚少。 工业界和组织工程师可能感兴趣的新型图案化蛋白质底物将首先被设计为在几何上控制肌肉细胞的生长和分化。 然后,在这些限定的基底上生长的单个细胞将被强行从基底上剥离。 各种光学显微镜将允许在纳米到微米尺度上进行定量分析。 一些营养不良型肌肉细胞的反应将与正常细胞进行比较,目的是补充和激励正在出现的基因治疗努力。 将寻求多个尺度的理论模型,包括不可扩展的胶带剥离模型和植根于分子力学的“分子”元素模型,以推进关于细胞膜力学和粘附的结构功能假设。为各个学术水平以及公众提出了更广泛的细胞和分子工程领域的补充教育计划。 实验室实习计划将为来自不同背景的本科生提供指导。 面向不同受众的新的动手细胞和分子工程实验室练习将补充本科生和研究生阶段工程课程的重点课程,并且一个公共访问互联网网站将致力于细胞和分子工程教育(http://www.seas.upenn.edu/~discher/cme.html)。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Dennis Discher其他文献
Effect of Nuclear Stiffness on Cell Translation In Vivo
- DOI:
10.1016/j.bpj.2010.12.1875 - 发表时间:
2011-02-02 - 期刊:
- 影响因子:
- 作者:
Takamasa Harada;Dennis Discher - 通讯作者:
Dennis Discher
Role of Mis Localization of DNA Repair Factors in Cell Cycle Arrest
- DOI:
10.1016/j.bpj.2018.11.454 - 发表时间:
2019-02-15 - 期刊:
- 影响因子:
- 作者:
Manasvita Vashisth;Sangkyun Cho;Dennis Discher - 通讯作者:
Dennis Discher
Mapping Protein Structure Changes with Cysteine Labeling Kinetics by Mass Spectrometry
- DOI:
10.1016/j.bpj.2011.11.3312 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Brian C. Chase;J. David Pajerowski;Diego Pantano;Hsin-Yao Tang;David Speicher;Dennis Discher - 通讯作者:
Dennis Discher
Matrix Rigidity Myosin-II and Lamin-A Regulate Curvature Induced Nuclear Rupture Causing Repair Factor Mislocalization and DNA Damage
- DOI:
10.1016/j.bpj.2017.11.2814 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Yuntao Xia;Jerome Irianto;Kuangzheng Zhu;Cory Alvey;Lucas Smith;Charlotte Pfeifer;Dennis Discher - 通讯作者:
Dennis Discher
Fibrillar Collagen is Equivalent to Stiff Matrix in Driving Marrow Stromal Cell Differentiation into a Matrix-Deficient, Myofibroblastic-Like Phenotype
- DOI:
10.1016/j.bpj.2012.11.3793 - 发表时间:
2013-01-29 - 期刊:
- 影响因子:
- 作者:
P.C. Dave P. Dingal;Matthew Raab;Palak Shah;Jae-Won Shin;Dennis Discher - 通讯作者:
Dennis Discher
Dennis Discher的其他文献
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{{ truncateString('Dennis Discher', 18)}}的其他基金
Nuclear Rigidity Scales with Tissue Elasticity and Directs Cell Fate
核刚性与组织弹性成正比并指导细胞命运
- 批准号:
1200834 - 财政年份:2012
- 资助金额:
$ 26.5万 - 项目类别:
Standard Grant
NanoMethods for Understanding How Matrix Elasticity Controls Stem Cell Mechanics & Differentiation
了解基质弹性如何控制干细胞力学的纳米方法
- 批准号:
0556259 - 财政年份:2006
- 资助金额:
$ 26.5万 - 项目类别:
Standard Grant
North American Research Fellows: Mechanochemical Determinants of Biomembrane Strength
北美研究员:生物膜强度的机械化学决定因素
- 批准号:
9505547 - 财政年份:1995
- 资助金额:
$ 26.5万 - 项目类别:
Standard Grant
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