Jorge Frias-Lopez, PhD

In recent years there has been an increasing interest on studying the composition of microbial communities living on the human body. This interest has crystallized in the Human Microbiome Project as a part of the NIH Roadmap.

 The human indigenous microbiota participate actively in a wide range of interactions with the host. However, their role on human health and disease remains largely unknown. Recent advances in DNA sequencing and the use of metagenomic approaches, which analyzes genetic information of the whole community instead of analyzing individual species, has opened the window to study complex microbial communities even when their members have never been isolated.  

The Frias lab focuses on studying the microbial ecology of microbial communities living within the human body, with special emphasis on the oral cavity. The overall goal of this research is to enhance basic knowledge on the role of the microbial communities on human health and disease.  

Multispecies biofilms as a model to expression in microbial communities   Microbes living on humans form biofilms that attached to different surfaces of the human body. A biofilm is a well-structured community of microorganisms that are usually encapsulated in a matrix produced by the organisms forming the biofilm. In the case of dental biofilms they are formed by up to 700 different species of bacteria. These biofilms are extremely complex, which makes its study in situ a challenging task. In vitro biofilm models have been used to simplify and gain understanding of such a complex community. We have developed an oral multispecies biofilm model that we use to study gene expression of the whole biofilm during the first stages of biofilm formation. Accumulation of bacterial subgingival biofilm is one of the main factors related to periodontal diseases. Basic knowledge of genes involved on the first stages of biofilm formation would allow us to target its formation and prevent the potential development of periodontal diseases.  

Metatranscriptomics: expression analysis of complex microbial communities  
Periodontitis is caused by the coordinated action of a complex microbial community, which results in inflammation of tissues that support the teeth. Periodontitis is responsible for half of all tooth loss in adults and is a widespread and serious health condition that occurs in moderate form in 30% to 50% of American adults and in severe form in 10% of adults. New metagenomic analysis has provided new insights on the composition of complex microbial communities. Quantitative molecular analyses of oral bacterial populations in healthy people and people with periodontitis has revealed an extremely diverse microbial community and demonstrated that disease progression is accompanied by a succession of different groups of bacteria. Nonetheless, in spite of our knowledge of community composition, there is a paucity of information about how genes in the community interact with each other and the environment. The use of metagenomic approaches has provided new insights on the composition of complex microbial communities. However, although metagenomics summarizes the composition of the microbial community, it provides only limited information on the activity of these organisms in the environment. It is their activity and interactions in the biofilm that control the pathogenetic activity of the microbial populations during periodontal disease. Therefore, the links between microbial community composition and pathogenic activity during periodontitis can be revealed through analysis of gene expression of the whole microbial community. Metatranscriptomics enables us to identify activities in complex microbial communities and to study the molecular mechanisms of complex polymicrobial diseases in situ. Defining the molecular mechanisms of pathogenesis would facilitate the development of novel, targeted approaches to prevent, diagnose and treat periodontitis, one of the most common and widespread human diseases. We are still at the first stages of using metatranscriptomics analysis to understand the complex interactions that occur in the microbial communities living within the human body, and tremendous work is still needed to develop the molecular biology and bioinformatic tools to make sense to such wealth of information.  

Our long-term goal is to understand the interactions that occur in complex microbial communities in the human body that lead to disease, focusing our efforts on the oral environment. Most importantly, the methods and concepts developed for the oral cavity can be applied, with minor modification, to study any other site within the body.

Selected Publications

Frias-Lopez J, Thompson A, Waldbauer J, Chisholm SW. (2009) Use of stable isotope-labeled cells to identify active grazers of picocyanobacteria in ocean surface waters. Environ. Microbiol. 11:512-525.  

Frias-Lopez J, Shi Y, Tyson G, Coleman M, Chisholm SW, DeLong EF. (2008) Microbial gene expression in the surface oceans. Proc. Natl. Acad. Sci. U S A 105:3805-3810.  

Klaus J, Frias-Lopez J, Bonheyo GT, Heikoop JM, Fouke BW. (2005) Bacterial communities inhabiting the healthy tissues of two Caribbean reef corals: spatial and interspecific variation. Coral Reefs 274:129-137.