Pattern formation & regeneration in a single cell

描述（由申请人提供）：细胞形成确定形状的能力，以及在损伤后动态再生其细胞骨架和膜结构的能力，是当前细胞生物学的一个未解之谜。除了是一个基本的细胞生物学问题外，了解细胞形态的发育和再生将是开发再生医学全新方法的起点，而不是试图用干细胞衍生的替代品替换受损细胞，而是诱导受损细胞在原位再生。目前，关于细胞如何产生和再生形态几乎一无所知。为了解决这个问题，我们转向一个经典的模型系统——巨型纤毛虫斯坦托。这种非凡的细胞足够大，可以进行显微外科手术，并且能够在几个小时内再生被切断的部分，恢复正常的细胞形状。我们将对Stentor基因组进行测序，并分析再生背后的遗传程序，以了解再生是否等同于正常形态发生的再激活或独特的修复机制，确定是否存在可定义的基因组模块，其激活可以在单个细胞水平上驱动再生，并探索细胞骨架和细胞内运输在再生反应中的作用。

DESCRIPTION (provided by applicant): The ability of cells to form defined shapes, and to dynamically regenerate their cytoskeletal and membrane structures following damage, is one of the current mysteries of cell biology. In addition to being a fundamental cell biological problem, understanding development and regeneration of cellular morphology would be a starting point towards developing a whole new approach to regenerative medicine, in which rather than attempting to replace damaged cells with stem cell derived substitutes, one would induce the damaged cells to regenerate in situ. Currently there is almost nothing known about how cells generate and regenerate morphology. To address this question, we turn to a classical model system - the giant ciliate Stentor. This remarkable cell is large enough to allow microsurgical manipulation and is able to regenerate severed parts in a few hours to restore a normal cell shape. We will sequence the Stentor genome and analyze the genetic programs that underlie regeneration, in order to ask whether regeneration is equivalent to a re-activation of normal morphogenesis or a distinct repair mechanism, determine whether there are definable genomic modules whose activation could drive regeneration at the level of a single cell, and explore the role of the cytoskeleton and intracellular transport in the regeneration response. PUBLIC HEALTH RELEVANCE: There is tremendous interest in regenerative medicine, i.e. approaches to restore human tissues and organs that have been damaged due to injury or disease. Most studies of regenerative medicine have focused on developing methods to use stem cells to replace damaged cells. We propose an alternative approach, which is to induce the injured cells to repair themselves. Towards this end, we will study a classical single-celled organism that has the ability to regenerate itself following damage.