Fuente: UM Newsdesk Articles on Science & Technology
Expuesto el: miércoles, 13 de junio de 2012 16:37
Autor: UM Newsdesk Articles on Science & Technology
Asunto: UMD Plays Key Role in Project IDing Bacteria that Cohabit Human Body
|
|
Genomic sequencing enables first reference data for microbes living with healthy adults
COLLEGE PARK, Md. -- Microbes inhabit just about everywhere in the human body. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with us and are in fact essential for our survival, providing vital metabolic services and supporting our immune systems. For the first time, a consortium of researchers organized by the National Institutes of Health has mapped the normal microbial make-up of healthy humans, producing numerous insights and even a few surprises. University of Maryland Professor Mihai Pop (Department of Computer Science, Center for Bioinformatics and Computational Biology, UMIACS) played a key role in this consortium, known as the Human Microbiome Project (HMP) Pop led a team of some 25 researchers from UMD, the Baylor College of Medicine, Broad Institute, Washington University in St. Louis, J. Craig Venter Institute, and Los Alamos National Laboratory in conducting a major step in the microbe gene sequencing process known as metagenomic assembly. Historically, doctors studied microorganisms in their patients by isolating pathogens and growing them in culture. This painstaking process frequently identifies only a few microbial species, as they are hard to grow in the lab. In HMP, researchers purified all human and microbial DNA in each of more than 5,000 samples and ran them through DNA sequencing machines. Using bioinformatic tools, researchers could sort through all 3.5 terabases of genomic data and identify specific signals found only in bacteria the variable genes of bacterial ribosomal RNA called 16S rRNA that can be used to identify microbial species. Focusing on this microbial signature allowed HMP researchers to subtract the human genome sequences and analyze only the bacterial DNA. UMD Computationally Piecing Togethe Bacterial DNA The key to analyzing the bacterical DNA lay in a process called metagenomic assembly. UMD's Pop led the team conducting this computational process through which the individual microbial DNA fragments are joined together to reconstruct larger segments of the bacterial genomes with which we share our bodies. "The data generated by the Human Microbiome Project exceeded in size and scope all previously generated metagenomic data sets," says Pop. "We knew a particular challenge was going to be the assembly of the nearly 7 terra base pairs (Tbp) of sequence information representing small fragments of the genomes of microorganisms found in and on the bodies of the HMP study participants." The metagenomic assembly working group led by Pop worked together over the period of close to one year to develop a strategy for the assembly of the HMP data and to generate assemblies for the almost 700 samples generated by the project. "The entire effort required tens of thousands of CPU hours, hundreds of emails, and weekly conference calls, and resulted in the creation of an unprecedented collection of data about the microbial communities that inhabit the human body," Pop said.
Together, Pop and the many other Human Microbiome Project researchers found, for example, that nearly everyone carries pathogens, microorganisms known to cause illnesses. In healthy individuals, however, pathogens cause no disease; they simply coexist with the rest of the microbiome and their human host. Researchers must now figure outwhy some pathogens turn deadly and under what conditions, likely revising current concepts of how microorganisms cause disease. The HMP is releasing its work in a sprawling series of coordinated scientific reports published online on June 13, 2012, in Nature and several journals in the Public Library of Science (PLOS). In these articles 200 members of the Human Microbiome Project (HMP) Consortium from nearly 80 multidisciplinary research institutions report on five years of research. Pop and his UMD colleagues are coauthors of two HMP papers appearing in Nature. Pop is also author of a perspective on the HMP work that is to appear in PLoS Computational Biology. The HMP, launched in 2007, received $153 million from the NIH Common Fund, a trans-NIH initiative that finances high-impact, large-scale research. Where doctors had previously isolated only a few hundred bacterial species from the body, HMP researchers now calculate that more than 10,000 microbial species occupy the human ecosystem. Moreover, researchers calculate that they have identified between 81 and 99 percent of all microorganismal genera in healthy adults. "We have defined the boundaries of normal microbial variation in humans, said James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning and Strategic Initiatives, which includes the NIH Common Fund. We now have a very good idea of what is normal for a healthy Western population and are beginning to learn how changes in the microbiome correlate with physiology and disease." HMP researchers also reported that this plethora of microbes contribute more genes responsible for human survival than humans contribute. Where the human genome carries some 22,000 protein-coding genes, researchers estimate that the human microbiome contributes some 8 million unique protein-coding genes or 360 times more bacterial genes than human genes. This bacterial genomic contribution is critical for human survival. Genes carried by bacteria in the gastro-intestinal tract, for example, allow humans to digest foods and absorb nutrients that otherwise would be unavailable. "Humans don't have all the enzymes we need to digest our own diet," said Lita Proctor, Ph.D., NHGRI's HMP program manager. Microbes in the gut break down many of the proteins, lipids and carbohydrates in our diet into nutrients that we can then absorb. Moreover, the microbes produce beneficial compounds, like vitamins and anti-inflammatories that our genome cannot produce. Anti-inflammatories are compounds that regulate some of the immune system's response to disease, such as swelling. Researchers were surprised to discover that the distribution of microbial metabolic activities matters more than the species of microbes providing them. In the healthy gut, for example, there will always be a population of bacteria needed to help digest fats, but it may not always be the same bacterial species carrying out this job. Moreover, the components of the human microbiome clearly change over time. When a patient is sick or takes antibiotics, the species that makeup of the microbiome may shift substantially as one bacterial species or another is affected. Eventually, however, the microbiome returns to a state of equilibrium, even if the previous composition of bacterial types does not. test12130 |
|
