When Dr. Rick Maizels began his doctoral research in immunology, little was known about parasites and so-called “neglected tropical diseases.” But as an increasingly prominent public health concern, vaccines and disease control were only the beginning. Research into our immunological response to infections showed that parasites were switching off their host’s immune system. For Dr. Maizels, that presented a promising biomedical opportunity.
Multicellular helminths are the most complex organisms to invade the human body. These parasitic worms cause widespread tropical diseases and exact a heavy toll on human health—greater than malaria and tuberculosis. They also pose fascinating biological questions. How do they evade the sophisticated mammalian immune system? And why are allergies and autoimmune disorders like Inflammatory Bowel Disease (IBD) more prevalent where parasites have been largely eliminated?
Follow the Molecules
Fast forward to September 2000 at the annual convening of the New Zealand Society for Parasitology, when Dr. Maizels found a kindred spirit in Dr. Danielle Smyth. They discovered a shared interest in the molecules secreted by parasites—something the field seemed to be overlooking.
Dr. Maizels grew up in London—one of three kids in an academic family. He was the only one drawn to scientific exploration, however, and he enjoyed being different that way. Science has continued to feed his appetite for breaking off in new directions. Like him, Dr. Smyth had two siblings and a taste for adventure that was encouraged by her engineer father. While her brothers followed in his professional footsteps, Dr. Smyth was torn between science and art. Once she recognized the creative possibilities of science—the beauty of organisms, the art of experimentation—she was hooked. Born in Brisbane, Australia, that also meant she would follow her father’s admonition to “go and see the world.”
The two researchers reconnected at a 2009 Keystone Symposia conference on the immunology of helminth infections. At the time, researchers had shown that parasites could significantly suppress IBD. Some were exploring the deliberate infection of humans with live parasites to reduce IBD’s inflammatory responses. Drs. Maizels and Smyth, however, were captivated by what caused that immunological effect. And that meant looking at the molecular signals parasites use to survive in our intestines.
Delivering on the Promise
Parasites can live in our gut for five years or more—a feat similar to successful tissue transplants. Understanding how they manipulate host immune response can reveal new avenues for controlling both parasites and the immune system.
Inspired by Rainin Foundation’s Innovator Awards, Dr. Maizels wanted to launch a new research initiative into treating IBD. Dr. Smyth’s earlier experience developing ulcerative colitis models made for a perfect partnership. So in 2013, Dr. Smyth joined the Maizels Lab at the University of Edinburgh. The lab moved to the University of Glasgow’s Wellcome Trust Centre for Integrative Parasitology in 2016.
Supported by three years of funding from the Rainin Foundation, the Maizels Lab aims to discover pharmacological methods for suppressing intestinal inflammation. With their microscopes trained on helminths, they’re testing novel approaches to harnessing the power of parasites. They have uncovered several molecules produced by parasites—largely proteins—that may be promising therapeutic candidates. But two big challenges will drive the next phase of their work.
The first is how to deliver the molecules. The second is that proteins might lose their efficacy if our immune system perceives and responds to them as foreign. Fortunately, new collaborators with possible solutions surfaced at an international conference.
Strengthening Research Worldwide
The scientific community boasts international networks of researchers who inform and strengthen each other’s work, often leading to new collaborations. As Drs. Maizels and Smyth travel the conference circuit, they encounter new ideas and share their own. They credit the Rainin Foundation’s Innovation Symposium for connecting them to investigators whose research could advance two therapeutic approaches.
In one case, transgenic algae developed by Rainin Foundation grantee John Chang with Steven Mayfield might offer a vehicle that people can take orally like a probiotic. A collaboration with Megan Levings and Laura Cook takes a different route, using cell-therapy to convert T cells into suppressive regulatory cells.
By discovering how parasites block intestinal inflammation, we also gain insights into how they survive and establish themselves. And that can translate into new therapies to both cure infections and treat immunological disorders. For Drs. Maizels and Smyth, molecules will lead the way.
The Kenneth Rainin Foundation is celebrating 10 years of formal grantmaking in 2019. To mark this milestone, we are sharing “10 Stories For 10 Years,” a series that pays tribute to the incredible work of our grantees and what we’ve learned along the way.