Cellular-scale superheroes

Tuesday, August 17, 2010 - 3:43pm
Jackie Johnstone

Tiny cancer-fighting superheroes are released into your blood stream. Their mission: to target a specific gene involved in over half of all cancers, interfere in the growth of cancer cells and eventually eradicate cancerous tumours - all with minimal side effects.

This is the vision of Professor Jumi Shin. These tiny superheroes are Shin's patented minimalist hybrid proteins - proteins she's designing to perform a very specific task - target the MYC gene.

I'm trained as a chemist, but I think of myself more as a problem-solver, says Shin, a specialist in biological chemistry at U of T Mississauga's Department of Chemical and Physical Sciences. For me it's about learning new techniques and seeking out collaborators to figure out how we are going to solve the problem.

Every cell in our body contains our full genome, but certain genes being turned on or off causes the cell to develop along different pathways. For example, among the cells in a fertilized egg certain genes get turned on at certain times, allowing for the creation of skin cells at one time and heart cells at another within a developing fetus.

Proteins have the ability to turn on or off genes by binding (or not binding) with our DNA, thereby regulating that gene's activity. Normally, the Myc protein regulates the expression of the MYC gene but a mutated Myc protein can knock this relationship out of balance, causing abnormal expression of the gene. The result is cell proliferation and, eventually, cancer. This Myc malfunction is involved in over 50 per cent of all cancers.

The specially designed proteins Shin is developing would compete with the Myc protein to regulate the MYC gene, preventing the Myc protein from binding and thus inhibiting the abnormal expression of the MYC gene.

Designing the most effective protein for this job, making it small enough to put into cells and developing the mechanism for delivering them to the right place are a few of the challenges Shin's team faces, but she is optimistic: Our preliminary results have been good. Our protein has been able to interfere with cancer cell growth in the laboratory.

If successful, a protein drug could also have far less side-effects than current cancer treatments. Chemo bombards the whole system, killing healthy and diseased tissue, whereas protein drugs can be very specific, allowing them to home in on the target and hit only the diseased cells, explains Shin, This could really minimize side-effects.

In Canada, there will be an estimated 173,800 new cases of cancer and 76,200 cancer-related deaths in 2010, according to the Canadian Cancer Society. An astounding 40 per cent of Canadian women and 45 per cent of Canadian men will develop cancer in their lifetime and 1 out of every 4 Canadians will die from it (based on recent incidence & mortality rates). Scientists have been fighting the war on cancer for over 40 years without an appreciable drop in the overall death rate of the disease.
Shin realizes the problem is a difficult one. It really is going to take a team of people with very different know-how to solve a problem as complex as this, she says, and you do actually need a big, diverse university environment to do it. U of T is great, fertile ground for this kind of modern, collaborative science.

She is working with a team of diverse researchers from across the University of Toronto. What we have here is a basic scientist, me, developing the minimalist proteins; Linda Penn, a cancer expert working at Princess Margaret Hospital in the University Health Network who will be testing these proteins in animal tissue; and Warren Chan, who is an engineer creating nanoparticles to act as delivery vehicles to bring these minimalist proteins into the cells.

The $750,000 dollar grant Shin and her team recently received from the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research, as part of the Canadian Health Research Project, ensures the collaborators can spend at least the next three years working full-time on their vision of a targeted anti-cancer protein drug - and bringing science closer to winning the war on cancer.