Mechanism of Cell Competition

? 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.