Mechanism of Cell Competition

 描述（由申请人提供）：本研究的长期目标是了解组织内特定细胞存活或消除的基础因素，以及它们如何影响移植和干细胞治疗（如应用于角膜）的成功。具体的目标是阐明最近发现的一种特定的转录因子对组织生长有新的影响。这种蛋白质延迟细胞的生长，改变蛋白质合成机制，并使其从组织中消除。使用突变果蝇的遗传上位性实验将被用来定义相关bZIP转录因子家族对细胞生长延迟和竞争性损失的贡献，部分采用对眼睛大小的影响作为测定。所选bZIP转录因子对基因转录的全基因组贡献将使用高通量测序方法在正常组织和具有蛋白质合成机制改变的组织中测定，目的是理解控制生长速率的调控过程和发生在嵌合体中以及可能在正常或癌性组织中的细胞之间的竞争。

 DESCRIPTION (provided by applicant): The long term goals of this research are to understand the factors that underlie the survival or elimination of particular cells within tissues and how they may affect the success of transplantation and stem cell treatments such as applied to the cornea. The specific goal is to elucidate the contribution of a particular transcription factor recently found to have a novel effect on tissue growth. This protein delays the growth of cells with alterations in the protein synthetic machinery and enables their elimination from tissues. Genetic epistasis experiments using mutant fruit flies will be employed to define the contribution of a family of related bZIP transcription factors to the growth delay an competitive loss of cells, in part employing effects on eye size as an assay. The genome-wide contribution of selected bZIP transcription factors to gene transcription will be determined using high- throughput sequencing methods both in normal tissues and in tissues with alterations in protein synthetic machinery, with the goal of understanding the regulatory processes that control the rate of growth and the competition between cells that occurs in chimeras and perhaps in normal or cancerous tissues.