Identifying novel strategies to promote tissue regeneration

确定促进组织再生的新策略

基本信息

批准号：
7647272
负责人：
Iswar K. Hariharan
金额：
$ 29.99万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2012-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Many adult human organs are incapable of repairing tissue that has been damaged as a result of injury or disease. Following myocardial infarctions, strokes and a variety of degenerative diseases, there is no effective way of replacing the damaged or lost tissue by regenerative growth. Hence, improving the regenerative capacity of adult tissues would dramatically impact the clinical management of these medical conditions. Remarkably, these same tissues can regenerate in animals such as the zebrafish and the newt. Since the same type of tissue can regenerate in one animal but not another, important differences must exist between similar tissues in different species that allow regeneration in one case but not the other. The challenge is to be able to find ways to manipulate tissue that lacks or has lost the capacity to regenerate to become capable of regenerative growth once again. The basic mechanisms that regulate embryonic development, cell cycle regulation and apoptosis were elucidated using genetic studies in Drosophila, yeast and C. elegans. However, until now, it has been difficult to use these model organisms to study the mechanisms that regulate tissue regeneration. We have recently developed a system that allows the tools of Drosophila genetics to be used to identify genes that regulate the capacity for regenerative growth. By expressing a gene that can kill cells in a manner that is both spatially and temporally restricted, we can efficiently ablate portions of Drosophila imaginal discs and allow them to regenerate in situ without the need for complex surgical manipulations. Regeneration occurs efficiently at specific stages of larval development but cannot occur beyond a critical point during the third larval instar. We propose to look for changes in the expression of regulators of growth and cell-cycle progression that correlate with the loss of capacity for regenerative growth. We will conduct a large-scale genetic screen for mutations in specific genes that can enable regenerative growth at later stages of development (at a time when it normally does not occur). Using this approach we aim to find strategies that can be used to enhance a tissue's capacity for regenerative growth. to Public Health This project is aimed at finding ways to get damaged tissue to be replaced by normal and functional tissue (regeneration). This would be important in the treatment of patients who have had heart attacks, strokes or degenerative diseases.

描述（由申请人提供）：许多成年人类器官无法修复由于受伤或疾病而受损的组织。在心肌梗死，中风和多种退化性疾病之后，没有有效的方法可以通过再生生长来替换受损或损失的组织。因此，提高成人组织的再生能力将极大地影响这些医疗状况的临床管理。值得注意的是，这些相同的组织可以在斑马鱼和纽特等动物中再生。由于相同类型的组织可以在一种动物中再生，而不是另一种动物，因此在不同物种的类似组织之间必须存在重要的差异，以便在一种情况下再生，而另一种情况则不得。面临的挑战是能够找到操纵缺乏或失去再生能力再次再生生长能力的组织的方法。使用果蝇，酵母和秀丽隐杆线虫中的遗传研究阐明了调节胚胎发育，细胞周期调节和凋亡的基本机制。但是，到目前为止，很难使用这些模型生物来研究调节组织再生的机制。我们最近开发了一个系统，该系统允许果蝇遗传学的工具用于识别调节再生生长能力的基因。通过表达可以以空间和时间限制的方式杀死细胞的基因，我们可以有效地消融果蝇想象的椎间盘的部分，并允许它们原位再生，而无需进行复杂的手术操纵。再生在幼虫发育的特定阶段有效地发生，但不能超出第三个幼虫龄的关键点。我们建议寻找与再生生长能力损失相关的生长和细胞周期进展调节剂表达的变化。我们将对特定基因的突变进行大规模的遗传筛选，该筛选可以在后期发育阶段（通常不发生）。使用这种方法，我们旨在找到可用于增强组织再生生长能力的策略。对于公共卫生，该项目旨在寻找使受损组织被正常和功能性组织取代的方法（再生）。这对于治疗患有心脏病，中风或退化性疾病的患者很重要。