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：
10614462
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/10614462
关键词：
Actins Adhesions Automobile Driving Biochemistry Biological Models Biophysics Cells Cellular biology Classification Complement Complex Computational Biology Computer Models Cytoskeletal Filaments Cytoskeletal Proteins Cytoskeleton Degradation Pathway Disease Drosophila genus Dynein ATPase Endosomes 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.

项目概要该 RM1 提案侧重于定义和描述支持的集成系统细胞内细胞器的运输和放置而不仅仅是将“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到细胞到体内水平的细胞器运输机制的理解。协作和多学科研究团队将发现和研究本土细胞和体外的微环境，通过考虑生理相关的组合分子马达、丝、接头、膜和其他控制细胞器的辅助因子我们将使用线粒体作为我们的初始模型系统，因为许多关键。对于该细胞器的动力学至关重要的分子和信号通路我们将揭示空间组织和动态的作用。细丝、机械力、运动活动和其他调节元件的组装将我们将在体外重建复杂的微环境以确定运动和我们将对这些系统进行计算建模并进行实验测试。我们的研究团队将通过直接在细胞和体内建立模型来获得活力和扩展。实施探索性试点研究计划，以纳入有前景的早期- 调查员加入我们的合作团队。