UNIVERSITY PARK, Pa. -- Two researchers in Penn State’s College of Agricultural Sciences have been awarded a grant through the Grand Challenges Explorations program, an initiative funded by the Bill & Melinda Gates Foundation.
Andrew Patterson, assistant professor of molecular toxicology, and Gary Perdew, John T. and Paige S. Smith Professor in Agricultural Sciences, will pursue an innovative global health and development research project, titled "Modulation of Aryl Hydrocarbon Receptor (AHR) Activity for Establishing and Maintaining Gut Immune Function and Overall Intestinal Health."
Grand Challenges Explorations (GCE) funds individuals worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges. Patterson’s and Perdew’s project is one of 107 Grand Challenges Explorations Round 8 grants announced this month by the Bill & Melinda Gates Foundation.
"Grand Challenges Explorations encourages individuals worldwide to expand the pipeline of ideas where creative, unorthodox thinking is most urgently needed," said Chris Wilson, director of Global Health Discovery and Translational Sciences at the Bill & Melinda Gates Foundation. "We’re excited to provide additional funding for select grantees so that they can continue to advance their idea towards global impact."
To receive funding, Grand Challenges Explorations Round 8 winners demonstrated in a two-page, online application a bold idea in one of five critical global heath and development topic areas that included agriculture development, immunization and nutrition.
Patterson and Perdew will lead a team of scientists to explore whether dietary modification or supplementation can produce nutrients in a mother’s breast milk that will enhance immune function in the gut of her children, with an eye toward reducing deaths and illnesses from gastrointestinal diseases.
"We believe that the aryl hydrocarbon receptor (AHR) is an untapped target for modulating intestinal inflammation and general intestine health -- one that will likely have far-reaching therapeutic implications," the researchers said in their grant application.
"We hypothesize that the delivery of natural AHR activators via breast milk will promote intestinal development and repair in newborns and young children, and bolster overall intestinal health in regions of the world where diarrhea and its associated complications are the second leading causes of mortality and morbidity."
The researchers explained that recent evidence strongly indicates that the AHR serves as a critical regulator of the gut immune function by maintaining the balance between immune suppressive regulatory’T cells and immune response promoting Th17 cells. In addition, they said, their unpublished data firmly indicates that the AHR plays a key role in the maintenance of barrier function, which influences the ability of bacteria to permeate the gut.
"A wide variety of AHR activators and precursors exist, including diet-derived nutrients, such as the essential amino acid tryptophan and various compounds that are obtained from green leafy vegetables," the researchers wrote. "These simple dietary modifications will likely result in maximum nutrient uptake and resistance to intestinal diseases for both the mother and child."
The grant will enable the researchers to prove their hypothesis first in a mouse model. In the future, they plan to extend the concept to human newborns and young children, eventually conducting intervention studies in settings where intestinal disorders in infants and children are common, such as in sub-Saharan Africa.
"Our approach represents an inexpensive, nontoxic and natural dietary means by which to pharmacologically target the AHR, the activation of which in the gut is critical for maximum immune surveillance and the promotion of improved intestinal barrier function," the researchers said.
About Grand Challenges Explorations
Launched in 2008, Grand Challenges Explorations is a $100 million initiative funded by the Bill & Melinda Gates Foundation. More than 600 people in 45 countries have received Grand Challenges Explorations grants. The grant program is open to anyone from any discipline and from any organization. The initiative uses an agile, accelerated grant-making process with short, two-page online applications and no preliminary data required. 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.