Faculty of Science News
Early Researcher Awards enhance projects of two scientists at Ryerson
By Megan O'Connor
November 24, 2014
Two Faculty of Science members won 2014 Early Researcher Awards (ERA) – a competitive fund provided by the Ontario government to help young researchers build their teams. Each will get $150,000 over five years. Dr. Catherine Beauchemin, in the Department of Physics, will develop her work on antiviral drugs to combat influenza. Dr. Roberto Botelho, in the Department of Chemistry and Biology, will expand his research on organelles. They both demonstrate the core criteria of the ERA: remarkable talent, and a project that gives back to society.
Influenza mutates rapidly. Vaccines for a new strain take six months to develop; in the meantime, many people will have been exposed to the virus. Antiviral drugs give us another important tool, and in the case of a flu pandemic will be our “first line of defence,” according to Beauchemin—a leader in the field of virophysics.
In Canada and Ontario, Tamiflu (generic name: “oseltamivir”) comprises 90 percent of our emergency antiviral stockpile. Sporadic resistance to Tamiflu in H1N1 and the possible emergence of resistance to bird (H5N1/H7N9) flu strains give us a warning bell—we may be relying too heavily on one drug—and indeed many countries (including Canada) are reviewing their antiviral stockpiling strategy. Beauchemin’s goal is to find “optimal cocktails”; to combine drugs in ways that deliver the most benefit to the patient, with minimum cost, while lowering the likelihood of emergence of resistant strains.
Beauchemin and her team develop mathematical and computer models (MCMs) that offer unique insight into how viruses spread cell-to-cell (i.e., within a cell culture or host). This spatial MCM is the first of its kind, and will enable her to explore factors that determine flu severity and spread. MCMs also enable her to test multiple drug combinations—a task that has proven too costly and time-consuming by experimental methods alone. Her team has already developed MCMs for two antivirals (including oseltamivir) used singly; by combining models, they can anticipate the effect of dual- and triple-therapy cocktails under different conditions—such as timing of treatment and severity or duration of flu strain.
“MCMs enable us to deconstruct a system into its components,” Beauchemin explains. “We can then look closely at how the pieces fit together to create the infection. If we can predict its course and outcome, we can ultimately control it.” Some of the “pieces” include the viral production rate and the infected cell lifespan. Antivirals act on one or more of these parameters, and yet resistance to each drug can happen rapidly during treatment; all it takes is for a single amino acid to mutate. MCMs offer a responsive tool.
Pandemic is not science fiction. Ontario needs a more robust preparedness plan, which Beauchemin and her team are working to inform.
Botelho’s projects are anchored by a single question: how do cells build themselves? His current work focuses on organelles, the cells’ very own organs—on how they acquire their identity and function. It’s a field of research that touches on medicine. When organelles fail, we get disease, inflammation, and auto-immune disorder. Botelho’s ERA project will look at a kind of organelle called a “lysosome” (found in animal cells); in particular, their role in immune function.
Botelho will build on research that was awarded CIHR funding in 2012 [link to 2012 article]. When our bodies detect a pathogen—an agent of disease—our white blood cells respond. They form a membrane that traps the harmful agent (e.g., a virus or bacterium). Sometimes, this “trap” will fuse with an enzyme-bearing lysosome that digests the agent. Botelho has found that activation of these cells causes lysosomes, which are ordinarily dot-shaped, to become tubular.
Botelho suspects that lysosomes—and the process of tubulation—are involved in antigen presentation (where an immune response is provoked by a molecule that the body perceives to be foreign). How do body cells respond to infection? And how do the pathogens—the source of disease—manipulate our body’s response? Botelho believes that insight into organelle change will lead to a deeper understanding of their role in the body’s defence: when it works and when it fails.
With his team of 13 researchers—from undergraduates to post-doctorate fellows—Botelho will look at how pathogens tamper with the immune cell’s ability to digest, and at how cells adapt to the presence of disease. Botelho is excited about a new line of query: “I’m now asking if immune cells, exposed to a pathogen, become better at dealing with infection,” he explains. “Do cells ‘scale up’ their ability to digest?” In other words, when a cell is exposed to a pathogen, does it somehow “teach” its genes that encode digestive enzymes to make more digestive enzymes and lysosomes? Botelho suspects they do. “It’s a temporary adaptation,” he adds. The scale-up occurs only in the presence of infection; once the signal of infection is gone, activity returns to former levels.
Yet insight into how it works may lead to new treatments; to research that informs how we manage infection, inflammation, and autoimmune disorders. Botelho’s ERA project will cast light on how lysosomes change in immune cells—a process that is critical for human health. It will pose longer term questions about whether pathogens interfere with lysosome tubulation, and about how lysosomes function in people with autoimmunity. And it will contribute to a wider understanding of organelle identity and function.
The title “early researcher” notwithstanding, Botelho and Beauchemin are becoming leaders in their field. Their work has been identified by the government as being strategically beneficial to Ontario, and lending itself to innovation. They are training the next generation of researchers. They also claim strong track records. In 2012, Beauchemin won the Macrae Group LLC Young Investigator Award. That same year, Botelho received the Maud Menten New Principal Investigator Award (biomedical theme) and a CIHR grant worth nearly half a million dollars. Recently, he was awarded a Canada Research Chair (Tier II). Funding at this level makes a real difference: it gives continuity (essential to long-term projects) and it ensures that young team members get time to develop their skills. Most of all, it raises the likelihood of impact – which, in the case of Beauchemin and Botelho, has implications for our health.
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