CAREER: Biophysics of Flatworm Regeneration

生物最有趣的方面是生物组织产生和保持其形状的能力。了解细胞如何能够创造出严格指定的三维几何结构的器官，将对生物医学(有助于解决癌症、再生和衰老)有很大的好处。更有趣的是，解码控制细胞行为的信号将深刻地增加我们对细胞功能的最基本属性和模式形成机制进化的理解。在这一领域取得进展需要一个模型系统--一种服从于分子时代最强大的细胞生物学和生理学技术的生物学背景。这项拟议中的工作围绕着一种令人着迷的有机体--爬行动物展开。这些自由生活的扁虫拥有一个真正非凡的特性：它们能够再生任何丢失的蠕虫碎片。基因组学方法正开始从生物化学的角度解决这一现象。有趣的是，初步数据表明，生物控制的一个新的生物物理方面负责蠕虫干细胞正确修复丢失组织的能力：关键细胞中的离子通道和泵的活动产生的自然电场。该项目将使用细胞和分子生物学方法来了解自然离子如何引导干细胞修复缺失的组织；各种学生和博士后研究员将参与其中。此外，扁虫代表了一种非常丰富但廉价的系统，用于向所有级别的学生介绍生物发现的基本方法。该项目包括一个重要的教育组成部分，它将创建一个基于网络的中心，向高中、大学和研究生实验室传播材料、方案和结果。拟议中的中心将点燃年轻科学家对生物模式深刻问题的兴趣，并为许多人提供参与并获得最先进技术实践经验的机会。

The most interesting aspect of living beings is the ability of biological tissues to generate and maintain their shape. Understanding how cells are able to create organs of a tightly-specified 3-dimensional geometry will have great benefits for biomedicine (helping to address cancer, regeneration, and aging). Even more interestingly, decoding the signals that control cell behavior will profoundly increase our understanding of the most basic properties of cell function and of the evolution of pattern-formation mechanisms. Making progress in this area requires a model system--a biological context amenable to the most powerful cell-biological and physiological techniques of the molecular age. The proposed work centers around a fascinating organism, the planarian. These free-living flatworms possess a truly remarkable property: they are able to regenerate any missing piece of the worm. Genomic approaches are beginning to address this phenomenon from a biochemical perspective. Interestingly, preliminary data indicated that a novel, biophysical, aspect of biological control was responsible for the ability of the worm's stem cells to correctly restore lost tissue: a natural electric field produced by the activity of ion channels and pumps in key cells. The project will use cell- and molecular-biological approaches to understand how natural ion flows direct stem cells to restore missing tissues; a variety of students and post-doctoral fellows will be involved. Additionally, the flatworm represents a very rich yet inexpensive system for introducing students at all levels to fundamental methods in biological discovery. The project includes an important educational component which will create a web-based center for the dissemination of materials, protocols, and results to high-school, college, and graduate student labs. The proposed center will ignite the interest of young scientists in profound problems of biological patterning and provide an opportunity for many to participate and gain hands-on experience in state-of-the-art techniques.