Dual Regulation of Phagosome Maturation in Tetrahymena

这个项目的灵感来自于100多年前发现的一个现象，即阿米巴原虫遇到一个粒子时，会吞噬并消化这个粒子，这一过程被称为吞噬作用。吞噬作用并不局限于阿米巴原虫，事实上，它是包括人类在内的许多细胞的基本活动。在这个项目中要解决的问题是，是什么决定了粒子被细胞吞噬后的命运？从许多研究中我们知道，被吞没的颗粒沿着一个独特的路线被传送，这个路线可以被描述为一组细胞隔间，每个隔间都有其独特的活动。在这个项目中解决的问题是：是什么定义了这些不同区域之间的发展？研究人员正在考虑两种基本模型。在第一个模型中，每个隔间都包含后续隔间的“方向”。在这个模型中，细胞内粒子运动的指令是固有的。第二个模型是基于隔室也可以在关键阶段从其他细胞结构获得线索的想法。特别是，研究人员假设一些隔室的特性是由它们所在细胞的邻近区域决定的。这项工作的重要性在于，它将帮助科学家了解这种基本的吞噬途径，而且它将有助于解决细胞如何组织其所有成分的更大问题。这个项目中的实验包括遗传方法，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微观镊子直接操纵细胞隔间。这些直接的方法使科学家们能够问，如果一个隔室被移动到细胞中的不同位置，它是否具有新的特性。本项目所进行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，学生将在细胞分析的遗传和物理方法方面发展专业知识。学生们还学习如何严格分析和清晰地展示他们的工作，包括口头报告和书面手稿。此外，预计当地高中生将在暑假期间参与这项工作。这些学生是通过大学赞助的少数民族机会暑期项目和当地一所高中的口口相传招募的，该高中的首席研究员是生物学咨询委员会的成员。首席研究员广泛致力于非专业人员的科学教育。他为非生物学本科生设计了一门广受欢迎的课程，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，特别是关于所谓“模式生物”的研究如何为广泛理解生物系统带来丰富的好处。

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.