Title: The role of reactive oxygen species (ROS) during tissue repair and regeneration
Supervisors: Professors Enrique Amaya and Ralf Paus, University of Manchester
Application deadline: January 30, 2015
There has been a resurgent interest in identifying the mechanisms by which various organisms are able to regenerate fully functional appendages and organs, as this information may help pave the way towards treatments in humans that better facilitate a regenerative response following injury. We recently found that appendage regeneration induces a sustained production of reactive oxygen species (ROS), and this production is necessary for appendage regeneration . The overall aim of this project is to investigate the regulation and role of ROS during tissue repair and regeneration, using a variety of model organisms, including Xenopus embryos and tadpoles, zebrafish larvae and human skin organ culture . Importantly, this project aims to determine the extent to which sustained ROS production is necessary for tissue repair and regeneration across different organisms, and whether an inability to produce a controlled and sustained increase in ROS levels may be associated with loss of regenerative capacity in mammals, including humans. A key question that needs to be addressed in pursuing this work will be to determine the mechanisms responsible for the production of ROS following injury.
The main questions this PhD project will aim to answer are:
1. What are the mechanisms that lead to the production of ROS following injury in various model organisms?
2. Is a role for sustained ROS production essential in tissue repair and regeneration across different model organisms?
3. What is the role of ROS production in adult human skin wound healing?
1 Love, N.R., Chen, Y., Ishibashi, S., Kritsiligkou, P., Lea, R., Gallop, J.L., Dorey, K. and Amaya, E. (2013) Amputation-induced reactive oxygen species (ROS) are required for successful Xenopus tadpole tail regeneration. Nature Cell Biology, 15:222-228.
2 Meier NT, Haslam IS, Pattwell DM, Zhang GY, Emelianov V, Paredes R, Debus S, Augustin M, Funk W, Amaya E, Kloepper JE, Hardman MJ, Paus R. Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin. PLoS One. 2013 Sep 2;8(9):e73596.
Further information: http://www.ls.manchester.ac.uk/phdprogrammes/projectsavailable/project/?id=1917