(Speaker Term: 7/1/12 - 6/30/14)
Director, Alkek Center of Metagenomics and Microbiome Research
Department of Molecular Virology and Microbiology
Baylor College of Medicine
One Baylor Plaza M.S. BCM280, Room 700B
Houston, TX 77030
Speaker’s URL: http://www.bcm.edu/molvir/index.cfm?pmid=15214
LECTURE TOPICS AND DESCRIPTIONS
The Human Microbiome: An Underappreciated Organ Important for Human Health
The microbes that colonize the human body (the microbiome) outnumber human cells by 10:1. The genes encoded by these bacteria outnumber the genes in the human genome by 100:1. We in the Alkek Center for Metagenomics and Microbiome Research (CMMR) are using metagenomic and systems biology approaches to better understand how the human microbiome contributes to our daily health. Among the questions being addressed are: is there a “core” set of organisms or genes that characterize the organisms that colonize everyone? How unique are the collections of organisms in each individual? How does our microbiome change over the course of our lives? How do diet, race, and gender impact the microbiome? How do human genetics shape the microbiome? And, conversely, how does the microbiome impact our daily health? Further, we are not limiting these studies to bacterial communities, but to viruses and microbial eukaryotes as well.
The Human Microbiome: Disease Associations Leading Toward Diagnostics and Therapeutics
Currently we are engaged in over 30 projects involving microbiome associations with human disease ranging from dry eye syndrome to nitrate reduction, and from alcoholism to cancer. In each case, changes in the microbiome associated with these diseases are being identified and leveraged for the development of diagnostics and therapeutics that may better diagnose and treat these ailments (or associated side effects and/or infections). Additional projects in animal models are focusing on hypothesis-driven research questions precipitating from our human studies.
Etiologic Agent Discovery Using Viral and Bacterial Metagenomics
We are using the technologies and approaches we apply to study microbial communities to discover etiologic agents for various diseases when traditional diagnostics fail. We are acquiring samples from cancer patients undergoing chemotherapy, with liver failure, with meningitis, sepsis, and high fever, among others, all with unknown etiologies. By sequencing these samples deeply, we are discovering agents potentially responsible for these infections that were missed by traditional diagnostics either because they were below the level of detection and/or the etiologies for these diseases are novel. By identifying new etiologic agents or identifying known etiologic agents with greater sensitivity, we will be creating opportunities for new diagnostics and treatment options for a variety of diseases.
Tadpole Diagnostics: A Platform for Sensitive Detection of Biodefense and Emerging Infectious Disease (Biod/EID) Pathogens
With collaborators at the Molecular Sciences Institute in Berkeley, CA, we have been developing protein-DNA chimeras to serve as sensitive reagents to detect pathogens, potentially to the single-cell level, in real-time PCR assays. The key to these reagents is the selection and affinity maturation of human antibody-expressing bacteriophage that bind key target proteins and carbohydrates on the surface of targeted bacteria, viruses, and parasites. We have developed a pipeline for evolving these antibodies with nanomolar binding affinities and are using them to detect Francisella tularensis and immune responses to Francisella in clinically relevant samples. This platform is now being retargeted toward other BioD/EID concerns and is in the process of being adapted for point-of-care use through the use of microfluidics and isothermal and rolling-circle DNA amplification strategies.
Comparative Genomics of Francisella tularensis (Ft): Toward Rationally Designed Live Attenuated Vaccines
Ft is a Category A biodefense concern. The Live Vaccine Strain (LVS) of Ft has served as a vaccine for Ft for the past 60 years in Europe and Asia, but is not licensed for use in the U.S. in part because its mechanism of protection in humans is poorly characterized and because the LD50 (lethal dose of bacteria needed to kill half of the animals in a given experiment) of LVS in mice by peritoneal injection is one bacterium. Furthermore, LVS is not protective against exposure to a large dose of organisms by inhalation as would be expected in a biological attack. We have sequenced the genomes of six important isolates of Ft and have identified mutations that distinguish highly-virulent and lesser virulent strains of Ft and other mutations that impact LVS attenuation. These mutations are being systematically evaluated for their attenuating potential, and those mutations found to be attenuating will then be used to create new rationally-designed mutants which will be tested in challenge animal models in the development of new, more protective Ft vaccines.
BIOGRAPHICAL SKETCH – Joseph Petrosino
Dr. Joseph Petrosino was hired as a tenure track faculty member at the Baylor College of Medicine (BCM) in 2006 with a National Institute of Allergies and Infectious Diseases-funded Career Development Award Project from the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease. As a result of his comparative genomics studies of Francisella tularensis, a pathogenic bacterium with the potential to pose a severe threat to public health and safety, the field has moved closer to the goal of creating new rationally-designed attenuated vaccines for this Category A select agent. In 2007, Dr. Petrosino and his colleagues procured funding from the NIH Common Fund Human Microbiome Project (HMP). As a large-scale sequencing center Principal Investigator for the HMP, Dr. Petrosino lead consortium efforts for standardized clinical sample preparation, sequencing, and analysis. This allowed microbial communities from diverse body sites and niches to be compared with minimal technical bias. As a result of the success of his efforts and to extend the efforts of the HMP, BCM announced the opening of the Alkek Center for Metagenomics and Microbiome Research (CMMR) in January 2011, with Dr. Petrosino serving as the Director for the Center. Currently, the CMMR is pursuing over 50 metagenomics projects in humans and model systems that target the improvement of human health through detection and modulation of the microbes that reside on and in us.
Assistant Professor – Baylor College of Medicine, Department of Molecular Virology and
Microbiology, Human Genome Sequencing Center, Department of Ophthalmology
Member – Cell and Molecular Biology, Translational Biology and Molecular Medicine programs, Baylor College of Medicine Diabetes and Endocrinology Research Center, and the Texas Medical Center Digestive Diseases Center.
ASM MEMBERSHIP AFFILIATION – Joseph Petrosino
Primary Division: N (Microbial Ecology)
Secondary Division: D (Microbe-Host Interactions)