CAREER: Signal Transduction of Eukaryotic Quorum Sensing

哺乳动物细胞感知周围细胞密度的能力在细胞生长控制和分化中起着重要作用。如果没有这种能力，发育中的胚胎将无法将其细胞适当地分成不同的组织类型。不幸的是，由于哺乳动物的复杂性，研究这种现象很困难。因此，本项目拟以社会变形虫盘状蝶形虫（Dictyostelium disideum）为模型，揭示和研究细胞密度感知的遗传调控。盘基骨柱细胞表现出哺乳动物细胞的许多特征，包括但不限于运动、分化、发育和细胞间信号传导。因此，它们是哺乳动物细胞行为的优秀模型，尤其是细胞密度传感。在饥饿的情况下，盘基ostelium细胞将经历一段时间的分化和发育，从而形成多细胞生物。然而，除非有足够数量的饥饿细胞形成一个完整的有机体，否则这个过程不会开始。因此，这些细胞能够感知周围饥饿细胞的密度，并做出适当的反应。这种感知是通过分泌和响应一种叫做条件介质因子（CMF）的蛋白质来完成的。随着越来越多的细胞挨饿，CMF水平上升，直到达到一个阈值水平，此时细胞能够开始发育。该项目将描述CMF水平如何被细胞感知并影响它们的发育决定。通过揭示CMF在盘状盘齿龙中的功能，可以更好地了解哺乳动物细胞中的细胞密度感应，从而更好地了解其在发育中的作用。这些实验将被纳入教学实验室，在那里本科生将参与到盘基骨菌突变体及其特性和操作的动手实验中。亨特学院有大量的少数民族学生，他们将参加这些实验室。

The ability of mammalian cells to sense the density of the cells around them plays an important role in cellular growth control and differentiation. Without such ability a developing embryo would be unable to properly proportion its cells into different tissue types. Unfortunately, studying this phenomenon in mammals is difficult due to their complexity. Therefore, this project is designed to uncover and study the genetic regulation of cell density sensing by using the social ameoba Dictyostelium discoideum as a model. Dictyostelium cells display many of the characteristics of mammalian cells, including but not limited to motility, differentiation, development and cell to cell signaling. Thus, they present themselves as excellent models for mammalian cell behavior, especially cell density sensing. When starved, Dictyostelium cells will undergo a period of differentiation and development leading to the formation of a multicellular organism. However, this process will not begin unless there are sufficient numbers of starving cells to form a full sized organism. Therefore, these cells are able to sense the density of the starving cells around them and respond appropriately. This sensing is accomplished by secreting and responding to a protein called Conditioned Medium Factor (CMF). As more cells starve, the levels of CMF rise until they reach a threshold level, at which point the cells are able to initiate development. This project will delineate how CMF levels are sensed by cells and impact their decision to develop. By uncovering the function of CMF in Dictyostelium discoideum, a better understanding of cell density sensing in mammalian cells can be gained, and with it, a better understanding of its role in development. These experiments will be incorporated into teaching laboratories where undergraduate students will participate in hands-on experiments with Dictyostelium mutants and their characterization and manipulation. Hunter College has a large population of minority students who will participate in these laboratories.