MassGeneral Hospital for Children receives grant to pursue novel antibacterial strategy

MassGeneral Hospital for Children (MGHfC) has been named a Grand Challenges Explorations winner through an initiative funded by the Bill & Melinda Gates Foundation. Led by Alessio Fasano, MD, MGHfC researchers Christina Faherty, PhD, and Stefania Senger, PhD—along with researchers at Massachusetts Institute of Technology (MIT)—will pursue an innovative global health and development research project, titled "Disarming Type III Secretion System of Enteric Pathogens."

Grand Challenges Explorations (GCE) funds individuals worldwide to explore ideas that can break the mold in solving persistent global health and development challenges. The collaborative project is one of more than 50 Grand Challenges Explorations Round 15 grants announced by the Bill & Melinda Gates Foundation. Initial grants of $100,000 are awarded two times a year. Successful projects have the opportunity to receive a follow-on grant of up to $1 million.

To receive funding, the MGHfC/MIT collaborators and other Grand Challenges Explorations winners demonstrated, in their two-page online application, bold ideas in one of five critical global heath and development topic areas. The foundation will be accepting applications for the next GCE round in March 2016.

The MGHfC research team led by Fasano is collaborating with MIT researchers led by Timothy Lu, MD, PhD, to develop pathogen-specific bacteriophages to "disarm" harmful bacteria such as Shigella flexneri. The pathogen causes a significant global health burden each year by causing millions of infections and significant mortality, predominantly in children under the age of five years in developing countries. There is no effective vaccine against Shigella, which is often transmitted in unsanitary settings. The recent rise of environmental enteropathy, a functional pediatric intestinal illness that does not respond to nutritional therapy, greatly accelerates the need for alternative therapies as well as successful vaccines.

After engineering the bacteriophage, the scientists will use an innovative research model—a novel human intestinal organoid (an artificially grown, in-vitro mini-organ) developed at the Mucosal Immunology and Biology Research Center (MIBRC) at MGHfC—to test the specialized "weapons." The bacteriophage will target the type-III secretion system to disarm the needle-like structure used to secrete proteins that help the pathogen infect and survive within the host. This targeted strategy will ensure the protection of beneficial bacteria, which are often affected by antibiotic treatment.

Fasano is the W. Allan Walker chair and division chief of Pediatric Gastroenterology and Nutrition at MGHfC. He also directs the MIBRC and the Center for Celiac Research and Treatment, which he founded in 1996. He holds the title of associate chief for basic, clinical and translational research in the Department of Pediatrics at Massachusetts General Hospital.

Provided by Massachusetts General Hospital