Project Title: In vivo analysis of skeletal regeneration in Zebrafish

Project supervisors: Dr Henry Roehl (BMS) and Ilaria Bellantuono (Human Metabolism)

Application deadline: Friday 14 December 2012.

Project description

One of the long-term aims of regenerative research is to provide methods to stimulate the body's innate ability to repair and regrow damaged tissues and organs. Unlike humans, zebra fish have an amazing capacity to regenerate many tissues and whole organs (eg eyes, heart, tail). It is known that fish and mammals use the same genetic pathways during development, so if we can determine which signals promote regeneration in fish, we may be able to apply these ligands to human patients to enhance repair.

We and others have found that fish bone repair involves dedifferentiation and proliferation of mature cell types (1,2). In addition, more recent study has implicated resident stem cells as a source of regenerative cells during tail repair (3). However these assays have been based upon amputation of the tail. Here we propose to develop a crush assay for adult bones (fin rays) that does not involve removal of tissue and is less disruptive. This assay has been piloted in our collaborators laboratory (Antonio Jacinto/ Gulbenkian Portugal) and preliminary data suggest that the repair mechanism is distinct from that of amputation (4).

Aims:

As in mammalian fracture repair, the bony rays of fish form a cartilage callous that is thought to stabilise the break and provide a scaffold for subsequent ossification. It is not known which genes are activated during this process. We will test which genes act during this early stage of regeneration focusing on signal transduction pathways.

References:

1. Sousa et al. Development 2011;138(18):3897-905
2. Knopf F et al. Dev Cell. 2011;20(5):713-24
3. Singh et al. Dev Cell. 2012;22(4):879-86
4.  Sousa et al. Biology Open, in press

Contact information:

Dr Henry Roehl

Web: http://www.shef.ac.uk/bms/research/roehl

Email: H.Roehl@sheffield.ac.uk