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.

Using an ENU mutagenesis screen, we identified several mutants with defects in the rapid growth and proliferation of cells in the developing digestive organs. When we cloned the underlying mutant genes, we found that they participated in essential cellular functions and the intestinal epithelial cells were undergoing programmed cell death.  

We used RNA-seq to identify the genetic pathways and cellular processes that are disrupted in each of the mutants. The next phase of this project is to explore why these pathways are so critical using cellular/molecular biology techniques and determine whether components of these pathways may be targeted therapeutically in cancer using disease models. 

 

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.

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.