Sensory studies with important implications
Genomicist Tiffany Timbers readily admits she prefers to concentrate her studies on nematodes (roundworms) and other invertebrates. Simply put, she said she finds the complexity of the mammalian nervous system “a bit overwhelming.”
The irony of that statement is that her work on nematodes can have significant effects on interpreting and understanding genetic mutations in humans, particularly the ones that cause disease.
The Banting post-doctoral fellow at Simon Fraser University summarizes her work as the study of how animals, including humans, see, taste and smell the world around us. She chose this career path because she loves “to learn new things about the world, as well as teaching new things to others.” An academic career, where she can do both, was an obvious fit.
When it comes to challenges, she said scientific research tests your patience and perseverance. “There were several times when I seriously questioned if this was what I wanted to do, and whether or not I could actually do it,” she said. “But, overall the good outweighs the bad and I am very happy I have been able to stick it out through the challenges.”
Her advice to other women in scientific research and high-powered computing is to break down all the challenges ahead — finishing your thesis or getting your next job, for example — into smaller tasks that don’t seem so overwhelming. Several small tasks, ultimately, lead to accomplishing those big-picture goals.
Her big-picture goal was to do exactly what she’s doing now: “I study how the external environment gets translated into the signal inside the cell,” she says. “To do that, I use a nematode worm. We use it because it has a very efficient and easy-to-use genetic model system. We easily can create thousands of genetic mutants.”
In the lab, she studies the ways in which these creatures sense their environments. When she finds one that has a problem, she looks at the whole genome sequence and tries to determine which gene is causing problems.
“Traditionally you’d use very labour-intensive genetic mapping experiments to do that, but instead, we decided to take a page from human genetics and try something similar to a genome-wide study approach,” she said. “Essentially, for each gene in the genome, we do a single test where we ask if the mutated form of the gene is more likely to be found in animals that have a certain characteristic/phenotype that we are interested in.”
Once she finds a mutation, she uses standard cell biology and genetic tools to prove that that gene is important for sensing the environment as well as to find out a little more about the gene’s function.
That process of doing the statistical test between the complex data set and phenotypes is where she uses Compute Canada’s resources. “This test could run on a much slower system,” she says. “But, it’s much quicker on Compute Canada’s system. I don’t think I could do the analysis without it. If I tried, it would take a really, really long time — much longer.”
So why should humans care how they sense the environment?
“If you look at cilia — they are structures within cells — that’s where the information is actually translated — from light, for example, into a chemical signal to receive that information,” she says. “Almost every single cell in the human body has one of these little cilia structures. For example, the cells in your kidneys have cilia they use to sense fluid flow and how iron concentrations are faring. These things are critical for kidney function.”
In the past couple of decades, researchers have realized that when patients have mutations in core cilia genes, they have a plethora of different ailments affecting all kinds of organs in the body: vision, reproduction, kidneys, heart function, organ placement and cognitive function.
“We work closely with human geneticist collaborators and it works in a reciprocal way,” Timbers explained. “We let them know about cilia genes and then, when they’re dealing with the patient cohorts and haven’t identified the gene causing the disease mutation, this can help them narrow in on new genes to look at for new mutations. Vice-versa, when their studies lead them to new genes and they work through their human and genetic mapping experiments, they can say ‘we have this patient who has this mutation in this gene, we think it’s causing the disease, but we have no idea what the gene does.’ Because the cilia structure is so well preserved, we can then go in and do the genetic and cell-biology studies to uncover its function.”
Timbers came to this interesting crossroads of biology and neuroscience after having completed an undergraduate degree in biology at Carleton University.
“I was very interested in genetics and animal behaviour,” she said. “I published my first paper there and became very interested in sensory biology. I wanted to stay with invertebrates.”
She knew about a researcher at the University of British Columbia who was looking at learning and memory so she applied to do her PhD in neuroscience there. After her PhD, she moved to Simon Fraser University to complete the postdoctoral research.
“I would like to become a professor,” she says. “I wanted to do a post-doc where I could keep the focus on cellular biology and interact with human geneticists.”