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.

知识分子的项目是受到100年前发现的一种现象的启发，即，在称为吞噬作用的过程中，遇到粒子的变形虫会吞噬粒子并消化它的事实。吞噬作用不仅限于阿米巴，但实际上是包括人类在内的许多细胞的重要活性。该项目中要解决的问题是什么决定了粒子被细胞吞没之后的命运？ 从许多研究中知道，吞噬的颗粒沿着独特的行程发送，该行程可以被描述为一组蜂窝室，每一个都有其独特的活动。该项目中解决的问题是：什么定义了这些不同的隔间之间的进展？ 研究人员正在考虑两个基本模型。在第一个模型中，每个隔间都包含后续隔室的“方向”。在此模型中，细胞内粒子进展的指令是隔室本身固有的。第二个模型基于这样的想法：隔室也可以从其他蜂窝结构中以关键步骤获取线索。特别是，研究人员假设某些隔室的性质取决于他们发现自己的细胞的邻里。 这项工作的重要性是，它将帮助科学家了解这一基本的吞噬途径，但它将有助于更大的问题，即细胞如何组织所有组件。 该项目的实验包括遗传方法，即分析有助于研究现象的基因，但还包括使用基于激光器的微观镊子直接操纵细胞室。这些直接的方法使科学家可以询问如果将新属性移至单元中的其他位置，该隔室是否会采用新属性。 对该项目的研究更广泛的影响将构成两名学生的博士培训的一部分，以及一名或多名本科生。由于项目的性质，学生将在遗传和物理方法上发展细胞分析的专业知识。学生还学习如何严格分析并清楚地介绍他们的作品，包括口头报告以及书面手稿。 此外，预计当地的高中生将在夏季参加这项工作。这些学生是通过大学赞助的少数派夏季计划和当地高中的口碑招聘的，该高中的首席调查员在那里担任生物学顾问委员会的工作。首席研究者广泛致力于非专家的科学教育。他教授了他为非生物学家本科生设计的广受欢迎的课程，处理了与大规模DNA测序相关的科学和社会问题。他将继续参与向公众提供研讨会，特别是关于使用所谓的“模型生物”的研究如何为对生物系统的广泛理解带来丰富的好处。