CAREER: Biophysical Mechanisms Underlying the Generation of Tissue Structure and Mechanics
职业:组织结构和力学生成的生物物理机制
基本信息
- 批准号:1751841
- 负责人:
- 金额:$ 50万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-06-01 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This Faculty Early Career Development Program (CAREER) research will develop new knowledge related to the structure and mechanics of living tissues and will train engineers to participate in bioengineering using targeted educational activities. The activities of genes direct the formation of tissues and organs but the proper shape, structure, and mechanical properties of the tissues are also guided by internal and external loading during development. It is known that abnormal tissue properties occur along with birth defects and cancer, but the extent that the abnormalities are genetic or occur from aberrant mechanical loads isn't known. It remains poorly understood how the mechanical and genetic factors work together to build normal tissues. The research will build an improved understanding of the underlying causes of birth defects and cancer by separating genetic from mechanical effects in tissue development. The work is an essential step toward the development of therapies to prevent or treat these diseases. The novel tools to control genetic expression and internal cell loading may also enable new strategies for tissue engineering and regenerative medicine, contributing to the progress of science and to the advancement of national health. The educational goal is to engage students from a variety of backgrounds in research. Ihe research will be integrated into: (1)opportunities for underrepresented minority high school students through the Columbia Engineering E.N.G. program; (2) career development and summer research mentoring for undergraduate women through the Columbia Engineering Summer@SEAS Program; and (3)a new course on Morphogenesis: shape and structure in biological materials aimed at introducing upper level undergraduate and graduate engineering students to research at the interface between mechanics and biology.The project will study several mechanics-based questions about the construction of tissues and organs, specifically how actomyosin-based tension is transduced through cadherin-based cell-cell contacts to regulate epithelial tissue morphogenesis. Three objectives are planned and include: (1) testing how tissue structure is controlled by forces, (2) determining the cellular rearrangements that drive cell shape changes, and (3) studying how these changes affect tissue mechanics. The research will advance fundamental understanding of how mechanical factors couple with biological factors to build and shape living tissues, filling a gap in our understanding of the role that mechanics plays in translating genotype to phenotype during development. The research will utilize the model organism Drosophila melanogaster and combine biomechanical and confocal imaging studies with systematic optogenetic manipulation of cellular force generation and mechanics in order to determine how tension generated by cellular actomyosin contractility and adhesion mediated by E-cadherin at cell-cell contacts control epithelial tissue shape, structure, and mechanics during embryonic development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
该教师早期职业发展计划(CAREER)研究将开发与活组织结构和力学相关的新知识,并将通过有针对性的教育活动培训工程师参与生物工程。基因的活动指导组织和器官的形成,但组织的适当形状,结构和机械性能也受到发育过程中内部和外部负荷的指导。已知异常的组织特性沿着出生缺陷和癌症,但是不知道异常是遗传的还是由异常的机械负荷引起的。 对于机械和遗传因素如何共同作用以构建正常组织,人们仍然知之甚少。该研究将通过将组织发育中的遗传效应与机械效应分开,更好地了解出生缺陷和癌症的根本原因。 这项工作是开发预防或治疗这些疾病的疗法的重要一步。控制基因表达和内部细胞负载的新工具也可能为组织工程和再生医学提供新的策略,有助于科学的进步和国民健康的进步。教育目标是让来自各种背景的学生参与研究。该研究将被整合到:(1)机会,代表性不足的少数民族高中学生通过哥伦比亚工程E.N. G。编程;(2)通过哥伦比亚大学暑期工程@SEAS项目,为本科女生提供职业发展和暑期研究指导;以及(3)关于形态发生的新课程:生物材料的形状与结构,旨在介绍高水平的本科生和研究生工程学生研究力学和生物学之间的接口。该项目将研究几个力学为基础的问题,关于组织和器官的建设,特别是肌动球蛋白为基础的张力是如何通过钙粘蛋白为基础的细胞-细胞接触转导,以调节上皮组织形态发生。计划了三个目标,包括:(1)测试组织结构如何受力控制,(2)确定驱动细胞形状变化的细胞重排,以及(3)研究这些变化如何影响组织力学。 这项研究将推进对机械因素如何与生物因素耦合以构建和塑造活组织的基本理解,填补了我们对力学在发育过程中将基因型转化为表型的作用的理解中的空白。该研究将利用模式生物黑腹果蝇,并将生物力学和共聚焦成像研究与细胞力产生和力学的系统光遗传学操作相结合,以确定细胞肌动球蛋白收缩性产生的张力和细胞-细胞接触时E-钙粘蛋白介导的粘附如何控制上皮组织的形状,结构,该奖项反映了NSF的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Using optogenetics to link myosin patterns to contractile cell behaviors during convergent extension
- DOI:10.1016/j.bpj.2021.06.041
- 发表时间:2021-10-05
- 期刊:
- 影响因子:3.4
- 作者:Herrera-Perez, R. Marisol;Cupo, Christian;Kasza, Karen E.
- 通讯作者:Kasza, Karen E.
Anisotropy links cell shapes to tissue flow during convergent extension
- DOI:10.1073/pnas.1916418117
- 发表时间:2020-06-16
- 期刊:
- 影响因子:11.1
- 作者:Wang, Xun;Merkel, Matthias;Kasza, Karen E.
- 通讯作者:Kasza, Karen E.
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