My name is Dr. Jason Berman and I am an investigator on two TFRI-funded projects: I am a member of the executive for Terry Fox PROFYLE (Precision Oncology For Young peopLE) and a part of the Li-Fraumeni Syndrome (LFS) Program Project Grant team.
For the past 11 years, I have overseen a unique zebrafish research program housed at the IWK Health Centre/ Dalhousie University in Halifax, Nova Scotia. Our current Zebrafish Core Facility is one of the largest of its kind in Canada and on par with the largest facilities in North America. We have the capacity to hold about 60,000 to 65,000 adult zebrafish, and right now we have about 20,000 to 25,000 fish in the system, which includes 80 different genetic varieties of zebrafish.
The zebrafish is a very useful model for studying genetic diseases, both inherited germline genetic diseases like Li-Fraumeni Syndrome(LFS), as well as acquired genetic abnormalities and somatic mutations like what occurs in cancers. There is a high level of genetic conservation between zebrafish and humans. About 75 to 80 per cent of genes are conserved at the protein level, which means that abnormalities that occur in humans can be mimicked in the zebrafish, which allows it to be a reproducible and reliable animal model. We have lots of tools to be able to manipulate the genes in zebrafish because the embryos are fertilized outside the fish and they are transparent. So we can easily see visual changes that occur because of these genetic manipulations, which makes the fish a fairly versatile, inexpensive, and useful tool to validate some of the genetic findings made by the LFS project's Toronto arm. In this project, we know that these patients have germline mutations in the p53 gene, a tumour suppressor gene, which makes these patients really akin to ticking time bombs. But it’s hard to predict what tumour they will develop when. If we understood what specific genetic abnormalities led to those problems, and what other pathways were activated, it would provide us with an ability to identify new drugs that we could use in that context. A system called CRISPR/cas9 allows us to precisely manipulate and introduce specific mutations into the zebrafish genome, which we couldn’t really do before, and using that approach we’re now introducing the most common p53 mutations found in Li-Fraumeni Syndrome into the zebrafish.
I think the other TFRI projects would be surprised at how conserved all these genes and proteins are in the fish, as well as how we can use these fish to look at drug responses just by adding the drug to the water. Further, drugs are metabolized in zebrafish the same way they are in humans, and we can also look at side effects. It really creates a whole platform to be able to do pre-clinical drug discovery in the fish. Doing this work with the support of TFRI highlights the capacity of the zebrafish system as a pre-clinical tool in cancer biology.
We’re really the only lab in Canada that uses the zebrafish to study cancer, and so by partnering with TFRI, and as part of the larger projects, it creates a highly collaborative, synergistic model. We want to help serve as a Canadian resource to help answer some of the critical questions in cancer research. It has really been instrumental to have TFRI support, and it is tremendously exciting to be part of these teams. There’s a lot of experimentation we can do alone with the zebrafish, but being a part of these teams is that much more rewarding.
Zebrafish facility at Dalhousie University
(Photos courtesy Berman lab)