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，是细胞生物学目前的奥秘之一。除了是一个基本的细胞生物学问题，了解细胞形态的发育和再生将是一个起点，朝着发展一个全新的方法，再生医学，而不是试图取代受损细胞与干细胞衍生的替代品，一个将诱导受损细胞原位再生。目前，几乎没有人知道细胞如何产生和再生形态。为了解决这个问题，我们转向一个经典的模型系统-巨大的纤毛虫Stentor。这个非凡的细胞足够大，可以进行显微手术操作，并且能够在几个小时内再生切断的部分，以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，以询问再生是否等同于正常形态发生的重新激活或不同的修复机制，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。 公共卫生相关性：人们对再生医学有着极大的兴趣，即恢复因受伤或疾病而受损的人体组织和器官的方法。大多数再生医学的研究都集中在开发使用干细胞替代受损细胞的方法上。我们提出了一种替代方法，即诱导受损细胞进行自我修复。为此，我们将研究一种经典的单细胞生物，它具有在损伤后再生的能力。

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.