The National Institutes of Health (NIH) has awarded scientists at Washington University School of Medicine (WUSM) four grants totaling $19 million to explore the trillions of microbes that inhabit the human body and determine how they contribute to good health and disease.
The grants are part of the Human Microbiome Project, an ongoing, ambitious effort to catalog the bacteria, viruses, fungi and other microorganisms that naturally coexist in or on the body. In all, $42 million in grants was awarded to 12 institutions.
The largest allocation -- $16 million – goes to Washington University’s Genome Center, which played a central role in the initial phase of the project. In the new effort, WUSM genome scientists, led by George Weinstock, PhD, will decode the DNA of about 400 microbes in collaboration with scientists at three other large-scale DNA sequencing centers. This information will then be used to catalog the microbes found in samples from healthy human volunteers to find out which microbes live in various ecological niches of the body.
WUSM researchers also received another $3 million for three pilot demonstration projects that investigate the link between changes in microbial communities and certain diseases. These one-year projects involve sampling the microbiomes of both healthy and ill volunteers. By comparing differences in microbial communities between the two groups, researchers hope to determine how microbes influence the risk of disease.
Gregory Storch, MD, the Ruth L. Siteman Professor of Pediatrics and director of infectious diseases at St. Louis Children’s Hospital, is working to uncover the full spectrum of viruses that cause sudden, high fevers in otherwise healthy children. His team will analyze blood samples and respiratory and gastrointestinal secretions from children with fever and healthy children to look for both known and new viruses. This information will provide a basis for understanding how viruses may contribute to fevers that cannot be traced to a recognized cause. Researchers will carry out similar studies in children whose immune systems are suppressed, either by HIV/AIDS and other illnesses or by medications related to organ and stem cell transplants.
Phil Tarr, MD, the Melvin E. Carnahan Professor in Pediatrics and director of pediatric gastroenterology, is investigating whether necrotizing enterocolitis, a devastating gastrointestinal illness that primarily affects premature infants, is linked to microbes in the intestinal tract. The condition affects about 10 percent of premature babies, usually in the first month of life, and is fatal in 15 to 30 percent of cases. Dr. Tarr and his colleagues are collecting fecal samples from premature babies to identify and quantify differences between the microbial communities of the infants who develop the illness and those who do not. This information may provide a foundation for developing ways to prevent or cure the illness.
Gastroenterologist Ellen Li, PhD, professor of medicine, is evaluating whether patients with Crohn's disease, a gastrointestinal illness that causes severe abdominal pain and diarrhea, have a genetic makeup that alters the types of microbes that colonize the intestinal tract. She and her colleagues suspect that mutations in the human genome combine with changes in the composition of intestinal microbes to cause the inflammation that is the hallmark of the disease.
Washington University's Genome Center also will collaborate on two additional pilot demonstration projects. One probes the link between the skin microbiome and acne in a project led by researchers at the University of California at Los Angeles. The other examines the microbiome of the urethra in adolescent males and its relationship to puberty, sexual activity and sexually transmitted diseases.
"Washington University is becoming a leader in a field that combines a high level of expertise in genome sequencing with physicians' intimate knowledge of disease," Weinstock says. "This large-scale effort will open doors in many areas of medicine to improve our understanding of good health and the treatment and prevention of disease."