Using Mouse Models to Understand Human Diseases

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By Shawn Lawrence

October marked the opening of a brand new building in the heart of Toronto’s famed Discovery District in the form of The Toronto Centre for Phenogenomics (TCP). Established with a vision to develop mouse models of human disease for the purpose of understanding the genetic basis of many human diseases, the research facility will be host to scientific collaborations discovering new knowledge and translating it into treatments to benefit people.

In this month’s edition of Across Canada, Biotechnology Focus goes one on one with TCP’s interim CEO, Colin McKerlie, to learn about the importance of the work being accomplished at the TCP, its mandate and what benefits the TCP will bring to its four member hospitals.

Q: What does Phenogenomics mean?

A: It’s really a combination of pheno-type and geno-type. We’re very interested here in the genetics of disease and with the genetics of disease when the genotype, which is all of the genes that we have as individuals goes wrong, it causes a phenotype – which is what the disease looks like. We’re bringing together phenotype and genotype, or as we call it ‘phenogenomics’.

Q: It’s been said that the Toronto Centre for Phenogenomics (TCP) is more than just a mouse house. What would you call it?

A: I’d call it a research-enabling centre. At the TCP, it’s all about human health research. There’s so much more than the mouse as a model system. It’s a research centre, that’s what we’re doing, that’s what we’re enabling for our four member hospitals and that’s what we’ll be doing for research in Toronto.

Q: What does the TCP bring to the Discovery District?

A: It definitely compliments all of the activity whether we’re talking about MaRs, which is kiddy corner to us and the whole concept of the Discovery District. The TCP is an important part of that cluster, its an important part of the enabling capacity of the Discovery District to really be a focus for health research for Toronto and also to be able to utilize that infrastructure and leverage it nationally.

Q: Is it primarily research and development that’s going to be done in here?

A: Big emphasis on the R, certainly yes to R+D. Our mandate is to support the research efforts in driving health research forward in our four member hospitals, Mount Sinai, St. Mike’s, Sick kids and UHN. We’re understanding basic biology, but of course we’re on a path to understand that basic biology, so we can understand disease when biology goes wrong and then we can take the next step into the development end and translation where we look to partner with industry and enable their efforts to turn this research into cures.

Q: What model systems are present at the TCP, mice and others?

A: The mouse is one of the model systems we use here and they live in the TCP. Another one of the big things that’s here is the mouse-imaging centre, where there is a lot of computer modeling and image analysis. Computer modeling is one thing we do a lot of. A lot of the model systems themselves are in-vitro; they’re on the bench such as molecular or cell-based systems.

Q: Where do the mice come from?

A: The mice typically come from suppliers of laboratory animals in the United States.

Q: What are some of the major diseases being targeted by TCP research?

A: Cancer, diabetes, immune system disease, nerve degenerative disease and of course a focus on pediatric specific diseases supporting the health research efforts of the hospital for sick children.

Q: What are some of the unique capabilities of the building and the facility?

A: We differentiate ourselves on a couple of levels in terms of the building. Firstly, it’s the largest building of its kind in Canada, and among the largest in the world. Another differentiator for us is the combining of the research labs with some of the support spaces, essentially bringing the researchers and the investigators who are trying to do their research into the common spaces that all the researchers have access to – the goal is to provide easy access to tools and technologies that all of the TCP community can use to accelerate their research efforts.

Q: How did the four hospitals come on board?

A: In 2001 Janet Rossant was the principal investigator and had a vision that for Toronto and for the discovery district, the academic science centres had to be able to participate and in some areas of the big science in the post genomic era; and to do that we needed more infrastructure, specifically a research enabling infrastructure that was likely beyond the reach of any individual member hospital. So it was after a lot of discussion with colleagues and principal investigators and scientists of the hospitals that we were able to bring them on board and really convince them that we needed a big building to help their research and to collectively enable the research across four member hospitals in a way that we hadn’t been able to before.

Q: How did you become involved
in this?

A: I was part of a group that with Janet shared the vision and believed that we needed to realize a building and infrastructure in a centre like the TCP.

Q: What attracted you to the TCP more than anything?

A: The capacity of the building to do great science and the concept of bringing people from four hospitals who are working on different questions together into a single space and start sharing ideas that can really accelerate some of the science and moving towards cures.

Q: How much was the cost of
the building?

A: It’s a $69,000,000 capital project. How it essentially breaks down is that it’s $49,000,000 in construction and $20,000,000 in equipment.

Q: Where is the funding for the TCP coming from?

A: Nationally from the Canada foundation for Innovation, provincially from the Ontario Innovation trust, and the remainder from the four member hospitals, with some incurring funds from industry.

Q: Do you see this collaboration growing beyond the four member hospitals and those currently involved with the development of the TCP?

A: Yes, it’s part of our mandate. Several of the research programs that are based at the TCP actually have a national mandate. We also have a particular partnership at the University of Toronto as an example where the Faculty of Medicine’s investigators will be utilizing some of the resources at the TCP.