Investigating mechanisms of cell death and survival using zebrafish

Investigating mechanisms of cell death and survival using zebrafish

Project details

Many genes that control embryonic development are found to be aberrantly expressed or disrupted in cancer. Our laboratory aims to identify genes that could provide novel targets for cancer therapy. To do this we employ the rapidly developing zebrafish intestinal epithelium as a surrogate tissue for bowel cancer growth. 

Using an ENU mutagenesis screen, we identified several mutants with defects in intestinal cell growth and proliferation. In three of these (flotte lotte, trinculo and perdita), the cells of the intestinal epithelium undergo programmed cell death. To understand the mechanisms driving this behaviour, the genetic pathways and cellular processes that are disrupted in mutant embryos were identified using RNA-seq. This project will explore why these pathways are so critical for intestinal epithelial (and potentially cancer) cell survival. 

 

Zebrafish section
Transverse sections of the intestine in a wild-type zebrafish (A) and a “cell death” mutant (B)
at 4 days of development.

About our research group

The Heath laboratory utilises zebrafish as a model for studying normal development and human disease.

As they are vertebrates, zebrafish have a high level of homology to humans in basic cellular processes such as cell signalling, protein trafficking, cellular architecture, cell migration and development. Zebrafish embryos are small, easy to manipulate and transparent. When combined with transgenes encoding fluorescent markers that label specific tissues, cells or proteins, it is possible to obtain high-resolution images of sub-cellular detail in living embryos. Finally, zebrafish are amenable to relatively straightforward genetic and epigenetic modifications, for instance using CRISPR/Cas9 technology.

All these techniques are used in the Heath laboratory to understand the mechanisms that contribute to the growth, proliferation and survival of developing tissues and cancer cells.

Researchers:

Karen Doggett in her office
Dr
Karen
Doggett
Development and Cancer division

Project Type:

Zebrafish swimming

Why are zebrafish increasingly used in medical research? Joan Heath writes in The Conversation.