An interdisciplinary team of Baylor College of Medicine and Texas Children's Hospital researchers will study the possible link between the human microbiome, the mitochondrial genome and premature birth with a four-year $600,000 grant from the Burroughs Wellcome Fund.

The grant is one of five nationwide designed to explore the biological mechanisms and causes of premature (preterm) birth, which occurs at a rate of 13 percent in the United States. Rates are even higher in African-American and obese populations.

Builds on genomic, metagenomic science

"Our funded Preterm Birth Initiative grant builds on Baylor's experience with genomic and metagenomic science, and extends that expertise into the realm of pregnancy," said Dr. Kjersti Aagaard, the principal investigator in the effort and assistant professor in obstetrics and gynecology at BCM. Aagaard is also a maternal-fetal specialist at Texas Children's. The effort flows from her work to determine how the health of the pregnant mother affects her developing fetus along with work on the Human Microbiome Project, which was key to developing the cohesive team behind the effort, she said. BCM is a part of the international effort to sequence the human microbiome, and was one of two clinical sites for the NIH Road Map (or Common Fund) initiative Human Microbiome Project (HMP).

"This is an important step for meaningful, novel research of high impact in the arena of preterm birth," said Dr. Ignatia Van den Veyver, vice chair for research in the BCM department of obstetrics and gynecology and a co-investigator.

Other investigators include Dr. James Versalovic, professor of pathology and immunology and molecular and human genetics at BCM and chief of pathology and director of the Microbiome Center at Texas Children's, Dr. Joseph Petrosino, assistant professor of molecular virology and microbiology at BCM, and director of the Alkek Center for Metagenomics and Microbiome Research at BCM, Dr. LuAnn Papile, professor of pediatrics-neonatology at BCM and director of developmental care and follow-up at the Texas Children's Newborn Center, Dr. Lee-Jun Wong, professor of molecular and human genetics at BCM, Dr. Aleksandar Milosavljevic, associate professor of molecular and human genetics at BCM, Dr. Yvette Johnson, assistant professor of pediatrics-neonatology at BCM and neonatologist at Texas Children's, and Dr. Toni-Ann Mistretta, senior biostatistician at BCM and Texas Children's. Versalovic, Aagaard, and Petrosino were co-investigators on the HMP JumpStart, which was initiated in 2007.

Extension of microbiome effort

"As director of the Texas Children's Hospital Microbiome Center, I support collaborations that lead to groundbreaking research in the science of the microbiome," said Versalovic. "The collaboration with Petrosino and Aagaard began with the initiation of the Human Microbiome Project here at Baylor College of Medicine. This is a natural extension of that effort."

"This research is among the first to ask pivotal clinical questions pertaining to birth-associated risks and the human microbiome," said Petrosino, an expert in the sciences of metagenomics and the microbiome.

The human microbiome is composed of the microbes that inhabit the human body. In fact, adult human have 10 times as many microbial cells as they do human cells. Some of these are helpful, others are benign and still others are potentially harmful. The Human Microbiome Project seeks to determine the genetic sequence of these different microbes with an eye to understanding and improving human health. Aagaard's current preterm birth initiative seeks to determine how the vaginal microbiome and the microbes it contains affect the risk of giving premature birth. Aagaard, Versalovic, Petrosino and their collaborators at BCM and Texas Children's Hospital have spent the last three years bringing together the massive clinical, and metagenomics sequencing and informatics infrastructure to enable this project largely through their interactions with the HMP.

"This environment of ‘big team science'—is so well fostered through Baylor College of Medicine, the Human Genome Sequencing Center, and Texas Children's Hospital—makes efforts such as these possible. It is just really amazing, cool science and I am lucky to have colleagues and support that make these studies possible," said Aagaard.

Sequencing, mitochondrial variations

The other facet of the research is sequencing and understanding the variations of the mitochondrial genome. Mitochondria are small organelles in each cell that produce energy. Once independent living cells, they become an integral part of human cells during the process of evolution. They are passed only from mother to child. In this study, researchers plan to determine the genetic sequence of the mitochondria of the mother, the fetus (from umbilical cord blood) and the placenta (the blood-rich organ that envelopes the developing fetus) and determine how they vary. Aagaard and her colleagues want to find out how variation in this important organelle might affect a mother's risk of giving birth prematurely and how it might interact as a susceptibility factor with the vaginal microbiome.

"Biological research is done in small steps," said BW Fund President John Burris. "It is our hope that by funding creative, innovative research, new therapies will be developed."

Other awardees include: Julie Baker, Ph.D., Stanford University, Genomic networks that guide trophoblast invasion and disease; Mala S. Mahendroo, Ph.D., University of Texas Southwestern Medical Center-Dallas, Assessment of cervical ripening by sodium magnetic resonance imaging; Jeffrey C. Murray, M.D., University of Iowa, Genomic signatures of gene expression and alternative splicing in preterm birth; Indira Mysorekar, Ph.D., Washington University, Occult infections in the etiology of preterm birth.

The Burroughs Wellcome Fund is an independent private foundation dedicated to advancing biomedical science through research and education.