Integrative mechanisms of organelle dynamics from the atomic-to-cellular level

从原子到细胞水平的细胞器动力学的整合机制

基本信息

批准号：
10396024
负责人：
ROBERTO DOMINGUEZ
金额：
$ 156.96万
依托单位：
UNIVERSITY OF PENNSYLVANIA
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：
2020-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10396024
关键词：
Actins Adhesions Automobile Driving Biochemistry Biological Models Biophysics Cells Cellular biology Complement Complex Computational Biology Computer Models Cytoskeletal Filaments Cytoskeletal Proteins Cytoskeleton Degradation Pathway Disease Drosophila genus Dynein ATPase Filament Goals In Vitro Interdisciplinary Study Kinesin Kinetics Mechanics Membrane Microtubules Mitochondria Modeling Molecular Molecular Motors Motor Motor Activity Myosin ATPase Organelles Organism Physiological Physiology Pilot Projects Positioning Attribute Regulation Regulatory Element Research Research Personnel Role Signal Pathway Structure Support System Testing cell growth regulation cell motility cofactor genetic regulatory protein in vivo mechanical force microsystems nanomachine organelle movement professional atmosphere programs reconstitution single molecule structural biology

项目摘要

PROJECT SUMMARY This RM1 proposal focuses on defining and characterizing the integrated systems that support intracellular organelle transport and placement. Rather than just characterizing “molecules” as biophysicists or “organelle dynamics” as cell biologists, our goal is to achieve an atomic-to- cellular-to-in vivo level understanding of the mechanisms of organelle transport. Our collaborative and multi-disciplinary research team will discover and study the native microenvironments in cells and in vitro, by considering physiologically-relevant combinations of molecular motors, filaments, adaptors, membranes and other cofactors that control organelle movement and polarization. We will use mitochondria as our initial model system, as many key molecules and signaling pathways that are essential for the dynamics of this organelle have already been described. We will uncover the roles of spatial organization and dynamic assembly of filaments, mechanical forces, motor activity, and other regulatory elements will be investigated. We will reconstitute complex microenvironments in vitro to determine motile and anchoring mechanisms. We will computationally model these systems and experimentally test models directly in cells and in vivo. Our research team will be energized and expanded by implementing an Exploratory Pilot Studies Program to incorporate promising early-stage- investigators into our collaborative team.

项目摘要该RM1提案的重点是定义和表征支持的集成系统细胞内细胞器的运输和放置。而不是将“分子”描述为生物物理学家或“细胞器动力学”作为细胞生物学家，我们的目标是实现原子能细胞到内的体内水平对细胞器转运机制的理解。我们的协作和多学科研究团队将发现和研究本地人通过考虑与物理相关的组合的细胞和体外微环境分子电动机，细丝，适配器，膜和其他控制细胞器的辅因子运动和极化。我们将使用线粒体作为我们的初始模型系统，作为许多关键对于该细胞器的动力学必不可少的分子和信号通路已经描述了。我们将揭示空间组织和动态的作用丝的组装，机械力，运动活动和其他调节元素将是调查。我们将在体外重新建立复杂的微环境，以确定运动和锚定机制。我们将在计算上对这些系统进行计算并实验测试直接在细胞和体内模型。我们的研究团队将通过实施探索性试点研究计划，以纳入有望的早期阶段调查人员是我们的协作团队。