Profile: Dr. Elizabeth Simpson

Of Mice and Men

You could call it a “happy” accident. In 2001, when Dr. Elizabeth Simpson was attempting to delete a specific gene in a mouse, she unintentionally recovered a second deletion.

The resulting impact on mouse behaviour was astonishing. Instead of displaying the usual meek behaviour, mice born without the second gene exhibited off-the-scale aggression. Dubbed “fierce” mice, they attacked each other and laboratory handlers without the slightest provocation.

Even more remarkable, when Dr. Simpson and her team later added the gene’s human counterpart to a strain of fierce mice, they found that their brains developed normally. The human gene appeared to
“correct” the fierce mouse’s pathological aggression.

“It was revolutionary. We had no idea that changing a single gene could have such a dramatic effect on behaviour,” says Dr. Simpson, a senior research scientist at UBC’s Centre for Molecular Medicine and Therapeutics and Canada Research Chair in Genetics and Behaviour.

The surprise findings propelled Dr. Simpson’s exploration of gene expression in mouse models into new areas, including a large-scale project funded by Genome BC and Genome Canada to develop genomic resources advancing therapies for brain disorders.

Led by Dr. Simpson, the international Pleiades Promoter Project team has spent the past four years building “MiniPromoters,” a set of genomics tools enabling the delivery of molecules to specific areas of the brain. By developing mouse models, it’s hoped these tools will eventually enable gene therapy for a host of brain disorders, including severe depression, multiple sclerosis, ADHD, and Huntington disease.

“The way gene therapy works right now, you can’t tweak one cell type of the

brain without hitting everything else. That’s what I want to change. What we’re

doing is creating switches, so that a therapy can be ‘turned on’ in only the cells

you want to target.”

So far, the team has built close to 140 new MiniPromoters for use in academic

and preclinical research, and is on track to meet its initial target of 200. One notable breakthrough has been the creation of a MiniPromoter that could be

used to allow certain therapeutics to temporarily cross the blood-brain barrier, which has historically presented a tremendous obstacle to drug companies developing treatments for brain disorders. “We’re really excited about this one.”

This past year, Dr. Simpson was awarded funding through Genome BC’s Science Opportunities Fund to make it easier for researchers and clinicians to use the tools they’ve developed, and to help the team to potentially join an international initiative using Brain MiniPromoters.

But it’s not all work and no play for Dr. Simpson. On most evenings and weekends, you’ll find her enjoying walks with her yellow labrador retriever, Taffy, and, in the winter, skiing at Whistler. She also shares season’s tickets for the Vancouver Canucks with a group of investigators, which guarantees tickets to about six games a year. But her true passion is running her lab.

“The brain is a special place and right now we’re not able to cure most brain disorders. Making gene therapy safe and effective will have a huge impact in the therapeutic realm.”

Genome BC’s Signals Summer 2009