All in the genes

All in the genes

Toronto researchers are looking to mouse genes to help them find lifesaving cures and treatments that can be transferred to humans
March 1, 2005
With the completion of the human genome sequence and now the mouse genome sequence, scientists discovered that people and mice share about 95 percent of their 30,000 genes in both sequences. That bumped up the cachet of the lowly mouse as a platform or model for researching human diseases and ultimately finding a treatment or cure for them.
 

At the Toronto Centre for Phenogenomics (TCP), they’re doing more than building a better mousetrap. They’re building a better mouse—one gene at a time.

In fact, researchers at the TCP—currently a virtual centre with its new home under construction and set for a 2006 launch—are making genetically modified mice and using specialized technologies to study how genes control basic biology, physiology, and behaviour. Genetically altered mice provide experimental models for studying human diseases, and finding new diagnoses and treatments. The future impact of this work will translate into better health outcomes for some of the most serious diseases worldwide.

“There are similar mouse centres in other countries, but none will have quite the same range of expertise and technologies under one roof,” says Dr. Janet Rossant, Professor of Biology at the University of Toronto. Her career-long research passion in this area of research will culminate with the TCP’s opening. “This is certainly one of the biggest and best mouse genetics centres in the world.”

By 2006, the TCP’s new home behind Toronto’s Mount Sinai hospital will be home to some of Canada’s top researchers. The researchers will be comparing the mouse genome and the human genome to find new cures for human diseases. The unique facility, shared by Toronto’s four main teaching hospitals in downtown Toronto, will incorporate the research programs of the Mouse Imagine Centre (MICe), the Canadian Mutant Mouse Repository, and The Centre for Modelling Human Disease, of which Rossant is the Director.

“This is not just about working with mice here in Toronto,” says Rossant. “It’s about providing a community resource to the worldwide community that uses the mouse as a model to study human disease.” Researchers will freeze embryos and sperm of genetically altered research mice for on-demand distribution to researchers elsewhere. The TCP will also provide services for clinical assessment of mutant mice to academic or industry researchers across the country.

“We recognized that a lot of the study for genetic diseases was going to be done in the mouse,” says Dr. Mark Henkelman, Director of the Mouse Imaging Centre and a Professor at the University of Toronto. “If you’re really serious about looking for human diseases in the mouse, you’d better have the same capacity for looking at diseases in the mouse as you do in humans.”

Henkelman says the trick was to develop specialized equipment such as “mouse MRI.” The people-sized machine lets researchers image up to a couple of dozen mice at the same time, expediting analysis. It’s especially useful when tracking minute changes in genetically identical mice, or when studying the effects of a particular genetic defect.

Benefits

A cancer patient lies in a hospital bed, his brain ravaged by a tumour, the clock ticking on his life. Doctors have one shot at possibly saving the patient with surgery, radiation, and a toxic cocktail of chemotherapy drugs. But which ones? What dosage?

 

“Brain tumours are really bad in that they are individualistic,” says Dr. Mark Henkelman, Director of the Mouse Imaging Centre (MICe). “Treatments are hugely toxic to the individual, so if we can be sure a particular treatment will work, that’s better than just picking one off the shelf and trying it.”

So how can doctors be sure they have the right treatment? Henkelman says new research just getting underway at MICe may soon help doctors pick the most effective treatment the first time around—by first testing various treatments on mice.

“You can actually take human brain tumour cells and put them in a mouse, which doesn’t have an immune system. Then you’re watching the human tumour grow using the mouse as a kind of substrate,” says Henkelman. That means doctors can first try out treatments on mice without risking human life, then go back and apply them as human treatments. With the short gestation period and lifecycle of mice, answers to profound medical problems may be found in just a few short weeks.

Henkelman says over the next 10 to 20 years this research could also lead to more effective and better targeted drugs. “If you could know up front which patient could tolerate which drug, we could probably use more effective drugs on specific subsets of the population,” says Henkelman. The approach is part of a new field of research called pharmacogenetics and one the earliest identified benefactors of mouse genome research.

“Essentially, the major breakthrough is the fact that we can mimic in the mouse any kind of genetic alteration that occurs in humans,” says Dr. Rossant. “There will soon be mice that have mutations in every gene in the genome, and that will really help us assess the whole function of genes. That’s the end goal of this research.”

Partners

The Toronto Centre for Phenogenomics (TCP) is going against convention and showing that research hospitals don't have to compete with each other in order to succeed. To make the TCP a success, four downtown Toronto teaching hospitals have come together in a unique research collaboration:

  • Mount Sinai Hospital.
  • The Hospital for Sick Children.
  • The University Health Network (the amalgamation of Toronto General Hospital, Toronto Western Hospital and Princess Margaret Hospital).
  • St. Michael's Hospital.

In addition to infrastructure funding from the Canada Foundation for Innovation, other funding partners for the TCP include the Ontario Innovation Trust, and the Ontario Research and Development Challenge Fund.

Learn More

For more information about the research organizations within the TCP: