In order to facilitate discovery of the roles that the microbiome plays in human health, nutrition, immunity, and disease, in 2007 the National Institutes of Health launched the Human Microbiome Project. Its mission was to generate the resources and expertise needed to characterize the human microbiome and analyze its role in health and disease. The NIH approved a budget of $170 million for this project over five years. This provided support for a number of centers and institutes around the United States, including one at Baylor College of Medicine, to serve as a "road map" for discovering the roles these microorganisms play in diverse niches of the human body.
The Alkek Center for Metagenomics and Microbiome Research (CMMR), based in the Department of Molecular Virology and Microbiology, was established in 2011 by Dr. Joseph F. Petrosino, a nationally recognized leader in metagenomic research, as an extension to Baylor's involvement in the Human Microbiome Project. The mission of the CMMR is to serve as an international hub for the development and implementation of advanced technologies for understanding how the microbiome impacts health and disease, and for the translation of this knowledge into microbiome-based therapeutics and diagnostics.
Researchers in the CMMR are developing molecular and bioinformatics tools and resources to advance numerous clinical and basic research projects pertaining to the organisms that comprise the microbiome, the genetic makeup of these bacteria, viruses and eukaryotes, and how this community of microorganisms interacts with human cells and tissues during the course of life.
The CMMR is actively involved in a great variety of projects that address the relationship between the microbiome and human disease, including irritable bowel syndrome, inflammatory bowel disease, Type 2 diabetes, leukemia, lung cancer, Crohn’s disease, among many others. A few of the research projects that focus on infectious diseases are summarized below.
Aberrant Microbe-host Communication Pathways Contribute to Rotavirus Disease
Interactions between microbes and their host use the same communication networks and pathways used to govern the day-to-day functions within our bodies. These communication pathways use an array of small molecules and cellular receptors to send and receive messages between cells and throughout the body. Some microbes co-opt these signaling systems to establish a stable home in our bodies, but many pathogens exploit these systems to benefit their growth and propagation. However, the aberrant nature of exploited signaling causes disease symptoms, including potentially life-threatening diseases like diarrhea.
Work in the laboratory of Dr. Joseph Hyser focuses on uncovering which of these communication pathways are important for supporting a healthy microbiome and which pathways are associated with diseases caused by pathogens, particularly viruses that cause diarrhea.
Most of the work uses time-lapse imaging of virus and bacterial infections of cells to watch and measure the change from normal to aberrant signaling using fluorescent sensors that are activated by important signaling molecules, such as Ca2+and cAMP. Using this technique, the scientists have discovered that rotavirus, a common diarrhea virus, activates hundreds of wide-spread aberrant signals through the secretion of ATP from a virus-infected cell to signal a neighboring uninfected cell.
Further, they have found that the extracellular ATP signal significantly contributes to the generation of rotavirus diarrhea. Therefore, new therapies that block this communication pathway may reduce rotavirus disease burden or deaths.
Extracellular ATP signaling is an ancient form of cellular communication, and rotavirus is the first virus identified to exploit this signaling pathway to increase its replication and cause disease. However, the Hyser Lab expects to identify other diarrhea-causing pathogens that exploit this or related pathways.