Title: The role and regulation of metabolic reprogramming during successful appendage regeneration
Supervisors: Professors Enrique Amaya and Royston Goodacre, University of Manchester
Application deadline: January 30, 2015
Many vertebrate species, including fish, amphibians and reptiles, have the ability to regenerate their appendages following amputation [1,2]. The regeneration process coordinates a variety of biological processes, all of which rely on molecules and energetic equivalents produced during cellular metabolism. Yet despite its intuitive importance, very little is known about how cellular metabolism is regulated during vertebrate tissue regeneration.
We recently found that the expression of a substantial number of genes governing glucose metabolism was greatly altered during Xenopus tadpole tail regeneration . These data and others have led us to hypothesize that glucose metabolism and its regulation plays an essential role during vertebrate appendage regeneration . Furthermore, we 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 carbohydrate metabolism during appendage regeneration, using Xenopus embryos and tadpoles as the model organism. More specifically we plan to explore the link between ROS production and metabolic reprogramming, in the context of tissue regeneration and embryogenesis. The main questions we wish to answer are:
1. Do embryos and regenerating tissues exhibit the Warburg effect, such that anabolic pathways are promoted?
2. What is the effect of ROS production on cellular metabolism in regenerating tissues?
3. What are the critical molecular targets of ROS that facilitate anabolic pathways during tissue regeneration?
This project will combine advanced in vivo studies with advanced metabolomic and proteomic analyses.
1 Brockes, J.P. and Kumar, A. (2008) Comparative aspects of animal regeneration. Annu Rev Cell Dev Biol 24: 525-49.
2 Sanchez Alvarado, A. and Tsonis, P.A. (2006) Bridging the regeneration gap: genetic insights from diverse animal models. Nature reviews 7: 873-84.
3 Love, N.R., Chen, Y., Bonev, B., Gilchrist, M.J., Fairclough, L., Lea, R., Mohun, T.J., Parades, R., Zeef, L. and Amaya, E. (2011) Genome-wide analysis of gene expression during Xenopus tropicalis tadpole tail regeneration. BMC Dev Biol 11: 70.
4 Love, N.R., Ziegler, M., Chen, Y. and Amaya, E. (2013) Carbohydrate metabolism during vertebrate appendage regeneration: What is its role? How is it regulated? BioEssays, in press.
5 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.
Further information: http://www.ls.manchester.ac.uk/phdprogrammes/projectsavailable/project/?id=1918