Dual Regulation of Phagosome Maturation in Tetrahymena

University Of Chicago, Chicago IL

Investigators

Abstract

Intellectual Merit This 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.