Dual Regulation of Phagosome Maturation in Tetrahymena

四膜虫吞噬体成熟的双重调节

• 批准号: 1051985
• 负责人: Aaron Turkewitz
• 金额: $ 67.42万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1051985&HistoricalAwards=false
• 关键词: Dual; Regulation; Phagosome; Maturation; Tetrahymena

Intellectual MeritThis project was inspired by a phenomenon discovered more than 100 years ago, namely the fact that an amoeba encountering a particle can engulf that particle and digest it, in a process called phagocytosis. Phagocytosis is not limited to ameba but, in fact, is an essential activity of many cells, including those in humans. The question being addressed in this project is, what determines the fate of a particle after its engulfment by a cell? It is known from many studies that engulfed particles are sent along a distinct itinerary that can be described as a set of cellular compartments, each with its unique activities. The question addressed in this project is the following: what defines the progression between these distinct compartments? The researchers are considering two basic models. In the first model, each compartment contains the "directions" for what the subsequent compartment will be. In this model, the instructions for the progression of the particle within the cell are inherent in the compartments themselves. The second model is based on the idea that compartments can also get their cues, at critical steps, from other cellular structures. In particular, the researchers hypothesize that the properties of some compartments are determined by the neighborhood of the cell in which they find themselves. The importance of the work is that it will help scientists to understand this basic phagocytic pathway, but also that it will contribute to the much larger question of how cells manage to organize all of their components. The experiments in this project include genetic approaches, that is, analyzing genes that contribute to the phenomena being studied, but also include directly manipulating cellular compartments using microscopic tweezers based on lasers. These direct approaches allow the scientists to ask whether a compartment take on new properties if it is moved to a different location in the cell. Broader Impacts The research pursued for this project will constitute part of the doctoral training of two students, and one or more undergraduates. Because of the nature of the project, the students will develop expertise in both genetic and physical approaches to cellular analysis. The students also learn how to rigorously analyze and clearly present their work, including oral reports and also written manuscripts. In addition, it is expected that local high school students will participate in the work during the summers. These students are recruited through a University-sponsored minority opportunity summer program and via word-of-mouth at a local high school, where the principal investigator serves on the Biology Advisory Board. The principal investigator is broadly committed to science education for non-specialists. He teaches a well-received course that he designed for non-biologist undergraduates, dealing with scientific and societal issues associated with large-scale DNA sequencing. He will continue to be involved in giving seminars to the general public, particularly on how research with so-called "model organisms" can yield rich benefits for the broad understanding of biological systems.

智力价值这个项目的灵感来自于100多年前发现的一种现象，即阿米巴遇到粒子时会吞噬粒子并将其消化，这一过程被称为吞噬作用。吞噬作用并不局限于阿米巴，事实上，它是许多细胞的一种基本活动，包括人类的细胞。这个项目要解决的问题是，粒子被细胞吞噬后，是什么决定了它的命运？从许多研究中得知，被吞噬的颗粒沿着一条不同的路线发送，这可以被描述为一组细胞隔间，每个细胞隔间都有其独特的活动。这个项目解决的问题如下：是什么定义了这些不同间隔之间的进程？研究人员正在考虑两种基本模型。在第一个模型中，每个舱室都包含下一个舱室将是什么的“方向”。在这个模型中，细胞内粒子前进的指令是隔间本身固有的。第二个模型是基于这样一种想法，即隔间也可以在关键步骤从其他细胞结构中获得线索。特别是，研究人员假设，一些隔室的性质是由它们所在的细胞所在的邻居决定的。这项工作的重要性在于，它将帮助科学家了解这一基本的吞噬途径，而且它还将有助于解决更大的问题，即细胞如何组织其所有组成部分。该项目中的实验包括遗传学方法，即分析导致正在研究的现象的基因，但也包括使用基于激光的显微镊子直接操纵细胞隔间。这些直接的方法允许科学家研究，如果一个隔室被移动到细胞中的不同位置，它是否会具有新的性质。这一项目所追求的更广泛影响的研究将构成两名学生和一名或多名本科生博士培训的一部分。由于该项目的性质，学生将在遗传和物理方法方面发展细胞分析的专业知识。学生们还学习如何严格分析和清楚地展示他们的作品，包括口头报告和书面手稿。此外，预计暑期将有当地高中生参加工作。这些学生是通过大学赞助的少数族裔机会暑期项目和当地一所高中的口碑招募的，那里的首席调查员在生物咨询委员会任职。首席研究员广泛致力于非专业人员的科学教育。他教授了一门广受欢迎的课程，这门课程是他为非生物学家本科生设计的，涉及与大规模DNA测序相关的科学和社会问题。他将继续参与为公众举办研讨会，特别是关于如何利用所谓的“模式生物”研究如何为广泛了解生物系统带来丰富的好处。