Investigating the beneficial role of OXPHOS during regeneration

In contrast to patients after myocardial infarction, fish can fully regenerate their hearts. However, not all fish are able to regenerate to the same extent, allowing comparative inter- and intra-species analysis to identify novel mechanisms controlling successful heart regeneration. We have compared the response of seven different wild type zebrafish strains as well as Astyanax mexicanus surface and cavefish to cryo-injury. Preliminary data shows that there are large differences in regeneration within each species. Using RNAseq, we have identifed OXPHOS as a crucial regulator of this difference with increased OXPHOS being beneficial to long term regeneration. This finding indicates that the current stance in the field, that OXPHOS is damaging the ability for heart regeneration, needs to be re-evaluated.

In this project, we will investigate the mechanisms underlying the beneficial role of OXPHOS during regeneration and the techniques you will perform are targeted metabolomics, QTL analysis, RNAseq and Electron Microscopy. As the human heart relies on OXPHOS for energy, the findings from this project could help identify therapies that can direct OXPHOS to enhance cardiomyocyte proliferation and harness the potential of the human heart to regenerate.