Grand Challenges

“Who among us would not be happy to lift the veil behind which is hidden the future; to gaze at the coming developments of our science and at the secrets of its development in the centuries to come?”

So asked the German mathematician David Hilbert in a lecture to the Second International Congress of Mathematics at the turn of the last century. Thereafter, he published a list of 23 foundational mathematical problems. The idea was that if the problems were posed, a community of people would strive to solve them. Some of the problems were solved, and some are still major mathematical conundrums.

The Gates Foundation has taken Hilbert as its model, creating a modern day list of seven goals to improve global health: to improve and create new vaccines, control insect vectors, improve nutrition, limit drug resistance, cure infection, and measure health status. After all, the Foundation explains, while much of today’s medical research does result in the creation of life-saving medicines, only a fraction of that research is on the development of tools to fight diseases that predominate in underdeveloped countries.

To facilitate the accomplishment of their seven goals, the foundation created the Grand Challenges Exploration grants. These $100,000 grants specifically promote innovation in the fields of medical research. Two recipients of this year’s grants are Notre Dame professors Jeffrey Schorey, associate professor of biological sciences and associate director of the Eck Institute of Global Health, and Kasturi Haldar, Julius Nieuwland Professor of Biological Sciences and director of the Center for Rare and Neglected Diseases (CRND). Both professors have developed innovative new ways to try and solve serious problems such as tuberculosis and malaria.

Both Schorey and Haldar value the support Notre Dame provides for work like theirs—through the CRND and Eck Institute, as well as through the Center for Social Concerns (CSC). Haldar in particular commends the priority of service on campus. “In addition to the CSC and CRND, the fact that Notre Dame students are committed to a high level of service enables the development of unique research and outreach programs in rare and neglected diseases,” she says.

In addition, Haldar and Schorey both value the ways in which the University and their institutes provide a forum for researchers from different fields. For Schorey, the Eck Institute “serves as a mechanism to bring people together in the area of global health. It facilitates research by facilitating that interaction.” Haldar thinks the small size of Notre Dame also has “helped foster collaboration with partners in science, engineering, social sciences, Arts and Letters, and the CSC. This is critical to developing a unique program in drug, vaccine and biomarker discovery, as well as a communications and educational hub to serve those who are struggling with disease,” she says.

Haldar’s journey to her current work began during her childhood in Mumbai, India, a country that had a reported 1.78 million cases of malaria in 2003. She came to the United States for her undergraduate education at Bryn Mawr, and stayed to earn her Ph.D. from MIT in biochemistry. She began work on malaria during her postgraduate research and continued the project when she came to Notre Dame.

While malaria has long been researched and there are well-funded vaccine programs in many countries, there is still no efficacious vaccine. Haldar takes a new perspective on this old problem: “A major obstacle has been the selection of suitable candidates from the hypothetical parasite genes whose function in infection remains poorly understood,” she explains. “Our approach has been to prioritize rational development of novel malaria vaccine targets, using rapid transgenic, cellular, and nanotechnology approaches to validate high-value candidate, hypothetical genes.”

Thanks to the Grand Challenges Grant, she and her lab will be able to develop five novel vaccine candidates against malaria, the group’s first effort at vaccine development. And since the deadliest of human malaria cannot be grown in laboratory animals like mice, she and her research assistants have been studying the human populations in endemic regions. More information on their previous research trips is available on her lab’s website.

Unlike the malaria Haldar investigates, tuberculosis can be beneficially studied in mice, although Schorey does anticipate having to visit endemic sites as well in the near future. Currently, he is working on the problem that has been his life’s work since his post-doctorate study at the Washington University School of Medicine. “When I was looking for a post-doc,” he explains, “I wanted to focus on something more immunological, disease-oriented, to feel a little closer to how my research can be applied.”

His choice to come to Notre Dame in 1998 has allowed him to, as he explains, wear many hats: he is a teacher, a researcher and, at the Eck Institute, an administrator. But what most fascinates him is his work on tuberculosis.

So what is he doing that has garnered him the Gates Foundation Grand Challenge Grant? His summary is—on the surface—simple: he and his lab are working to find a new, more effective, vaccine for tuberculosis.

To do this, however, he is reworking the idea of a tuberculosis vaccine from the ground level. He explains the process, beginning with the invasion of microbacteria into the microphage, the cell essential to fighting off infections. This causes the microphage to release membrane vesicles. These vesicles are, he says, like soap bubbles that contain microbacteria components, as well as antigens that are known to incite a strong immune response against the microbacteria. His plan is to isolate these soap bubbles, or lipids, and use them as a vaccine. Once administered, they work as a teaching aid to the body, showing it both the infection and how to fight it in one step.

But why is this particular vaccine necessary—why TB? Schorey rolls off some basic facts: there are 8 million new cases, and 1.7 million deaths every year. It is the leading cause of death in HIV patients and people with compromised immune systems, worldwide. And one third of the world’s population is infected with TB—over two billion people.

But Schorey is motivated by more than simple statistics. The statistics support a deeply held need to apply the research he has spent his life conducting. “I think the whole reason many of us get into working on these diseases is because you can’t help it—you see these people die every few minutes from diseases that are really preventable—it just pulls on you and so you want to do something and if this works, I’ll do something,” he says.  

Haldar agrees. “There is a moral imperative to try to develop and deliver therapies that are currently possible, and build capacity at these sites so they can sustain their own research and therapeutics programs,” she says. Now, with these new grants, both Haldar and Schorey can continue trying to solve the world’s problems. 

For more information on the Gates Foundation Grand Challenges Exploration Grants, visit the website.