Administrative supplement for the purchase of a confocal microscope

购买共聚焦显微镜的行政补充

基本信息

批准号：
10797113
负责人：
Panagiotis Mistriotis
金额：
$ 25万
依托单位：
AUBURN UNIVERSITY AT AUBURN
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-10 至 2027-06-30
项目状态：
未结题

项目摘要

Contact PD/PI: Mistriotis, Panagiotis Summary: Cell migration is a fundamental cellular phenomenon that plays a pivotal role in (patho)physiological events, including organ development, tissue regeneration and cancer metastasis. Our long-term goal is to achieve a comprehensive understanding of the mechanisms of cell migration in order to develop novel therapeutic tools and strategies to prevent the initiation and progression of diseases, including cardiovascular pathologies, aging, and cancer. Building on the PI's postdoctoral work, the lab explores how the physical cues of the local microenvironment (e.g., confinement, viscoelasticity, stiffness, pressure and shear stress) convert into biochemical signals to influence the migratory behavior of cells. Over the next five years, we will employ state-of-the-art microfabricated devices, materials, optogenetic tools, single-cell transcriptomics and computational simulations to elucidate the effects of pressure forces on cell migration and viability. The scientific premise of this application is based on prior studies showing that cells experience elevated pressure forces during various stages of migration and invasion, including extra/intravasation and interstitial migration. Although the widely held view is that cells can adapt to mechanical cues, an open and unaddressed question is how elevated pressure affects cell behavior in diverse, yet physiologically relevant, microenvironments. To answer this question, we will investigate the interplay between pressure forces and different microenvironmental cues (physical or biochemical) in the regulation of cell migration. We will also assess whether long-term cell exposure to high pressures alters the sensitivity of cell motility to physical cues. Last but not least, we will dissect the relative roles and potential crosstalk between confinement and pressure in cell death regulation. Taken together, the proposed studies, which are supported by highly encouraging preliminary results, will delineate the underlying mechanisms regulating cell behavior in physiological environments and generate novel conceptual information that will facilitate the identification of new therapeutic targets aimed at promoting or preventing cell motility in vivo. Project Summary/Abstract Page 6

联系PD/PI：Mistriotis，Panagiotis 摘要：细胞迁移是一种基本的细胞现象，在（PATHO）生理中起关键作用事件，包括器官发育，组织再生和癌症转移。我们的长期目标是对细胞迁移的机制进行全面的了解，以发展新颖治疗工具和策略，以防止疾病的启动和进展，包括心血管病理，衰老和癌症。在Pi的博士后工作的基础上，实验室探索了物理线索局部微环境（例如，限制，粘弹性，刚度，压力和剪切应力）转换进入生化信号以影响细胞的迁移行为。在接下来的五年中，我们将雇用最先进的微制设备，材料，光遗传学工具，单细胞转录组学和计算模拟以阐明压力力对细胞迁移和生存能力的影响。科学该应用的前提是基于先前的研究表明，细胞经历了升高压力在迁移和入侵的各个阶段，包括额外的/侵入和间质迁移。虽然人们普遍认为，细胞可以适应机械提示，一个开放且未解决的问题是如何升高的压力会影响各种但与生理相关的微环境的细胞行为。回答这个问题，我们将研究压力和不同微环境线索之间的相互作用（物理或生化）在细胞迁移的调节中。我们还将评估长期的细胞暴露高压会改变细胞运动对物理线索的敏感性。最后但并非最不重要的一点，我们将剖析在细胞死亡调节中，限制与压力之间的相对作用和潜在的串扰。在一起，拟议的研究得到了极大鼓励的初步结果的支持，将描述调节生理环境中细胞行为的基本机制并产生新颖的概念将促进旨在促进或预防细胞的新治疗靶标识别的信息体内运动。项目摘要/摘要页面6