Multiomic Approaches to Study Host Pathogen Interactions

摘要

Over the last several decades, research into the causes and pathophysiology of infectious disease has become a major focus in order to allow for the development of novel treatment and prevention modalities. During that period of time, the developmentof novel research tools has allowed for the continual improvement in our understanding of these disease processes. Improvements in our ability to cultivate both bacterial and viral organisms played a critical role in the initial identification of a significant number of etiologic agents and improved our ability to diagnose disease. Later, the development of the polymerase chain reaction (PCR) methodology revolutionized diagnostics and allowed for the basis of our modern diagnostic systems that rely heavily on that technology. Likewise, PCR opened the door for the development of real-time reverse transcriptase PCR and allowed, for the first time, the ability to monitor mRNA levels and gene expression of individual gene targets. The development of Sangerbased DNA sequencing gave us the ability to sequence portions of both the bacterial and host genomes, however the complexity of the genomes along with the lack of good bioinformatics support (both computer power and bioinformatics tools) maintained theresearch at a relatively slow pace. During the last decade the development of microarray technology allowed for the simultaneous comparison of gene expression across a larger subset of know gene targets. While all of these technologies have contributed greatly to improving our understanding of the pathophysiology of disease, they have in large part not allowed for the large-scale systems level approach that would allow the global picture of how the host and pathogen interact and impact one another. Alsolacking was an appreciation of the fact that the pathogens are present, not as a monoinfectious process, but instead are part of a much more complex microbial community whose members also influence pathogen colonization, growth and replication. The recent development and rapid advancement of next generation sequencing methodologies have for the first time opened to door to a more comprehensive "systems-based" approach to studying the host-pathogen interaction at a molecular scale. These technologies have allowed for whole genome scale studies, on both the pathogen and host side, as well as providing a means by which to look at the bacterial and viral microbial communities on a global scale. As such, the simultaneous application of several next generation based sequencing technologies to models of infectious disease is opening new avenues of research and holds to potential to impact animal health at levels never reached before. The goal of this presentation is to provide the audience with an appreciation of the new technologies and how they can be applied to study pathogen-host interactions on a systems level. While the technical aspects of the process are far beyond the scope of this presentation, we will focus on the basic principles and approaches used in this type of research.