Whole genome screen for novel regulators of tissue homeostasis and regeneration Schmidtea mediterranea is a model system for addressing human health issues. Planarians are well known for their ability to regenerate complete animals from fragments of their bodies. Following recent demonstrations that S. mediterranea is amenable to modern cell, molecular, and RNAi techniques, it is becoming the model organism of choice for addressing research questions that cannot be easily studied in Drosophila melanogaster or Caenorhabditis elegans, including wound healing of adult tissues, regeneration, somatic stem cells, and tissue homeostasis. In 2007 we annotated the S. mediterranea genome and constructed a publicly available genome database, SmedGD containing the gene models. The objective of this grant is to use the S. mediterranea gene annotations in a high-throughput image-based screen for novel regulators of tissue regeneration and homeostasis. Toward this end we will (1) employ a battery of molecular and immunological techniques, including a genome-wide RNAi screen, and (2) leverage existing image processing, management and annotation tools to construct a cyberinfrastructure that can both support our experiments and distribute our results to the scientific community.
This project will use the sequenced genome of the planarian Schmidtea mediterranea to search for genes involved in tissue maintenance and regeneration. The project employs a number of exciting new technologies, including RNA interference, an automated confocal microscope, and image processing and annotation tools to achieve its aims. Because we will restrict our screen to planarian genes with bona fide human homologs, any stem cell function deficiency phenotype obtained becomes a potential model to study human stem-cell function, regeneration and wound healing, effectively advancing efforts in these frontiers of human health.
|Keefe, Alexandra C; Lawson, Jennifer A; Flygare, Steven D et al. (2015) Muscle stem cells contribute to myofibres in sedentary adult mice. Nat Commun 6:7087|
|Murphy, Malea M; Keefe, Alexandra C; Lawson, Jennifer A et al. (2014) Transiently active Wnt/?-catenin signaling is not required but must be silenced for stem cell function during muscle regeneration. Stem Cell Reports 3:475-88|
|Flygare, Steven; Campbell, Michael; Ross, Robert Mars et al. (2013) ImagePlane: an automated image analysis pipeline for high-throughput screens using the planarian Schmidtea mediterranea. J Comput Biol 20:583-92|