The advent of high-throughput genomics and associated technologies have afforded the ability to begin to ask detailed questions about the biology of whole systems, rather than examining parts of the system in isolation. This application contains studies that explore the dynamic interactions between pathogens, hosts, their microbiota, the immune system, and the environment, with the goal to provide a more comprehensive understanding of the determinants of infectious disease outcome. The projects target high priority viral, bacterial, fungal, and parasitic pathogens in relation to unique sets o samples from human subjects, when possible, as well as relevant animal models of disease, as appropriate to each project. Pathogens often subvert host cells by using their gene products to manipulate cellular pathways for survival and replication; in turn, host cells respond to the invading pathogen through cascading changes in gene expression. Deciphering these complex temporal and spatial dynamics to identify novel virulence factors or host response pathways is essential for full understanding of the infectious disease process. The integration of the high-throughput technology with the biological question highlights the evolution of genomics as an area of research from a strictly observational tool of only a few years ago, to being an integral part in the examination of the disease process and human health as a whole. The genomic viewpoint is becoming more complete, as we can begin to simultaneously characterize the interactions of host, pathogen and microbiota. The integration of the data from these complex interactions is providing the foundation for a deeper understanding of health and disease. This proposal includes a highly collaborative group of investigators centered within the Institute for Genome Sciences at the University of Maryland who are experts in their respective areas of pathogen biology, but also are pioneers in the field of genomics. We expect that these studies will address major gaps in knowledge related to the molecular pathogenesis of viral, bacterial, fungal and parasitic pathogens and in host responses to infection. RELEVANCE: Infectious diseases cause significant morbidity and mortality around the world. The work described in this application will use current genomics-based approaches to reveal new information about disease-causing agents and the hosts that they infect. The scientific community will be able to use the results of these studies to design better diagnostics, anti-microbial compounds and vaccines. Project 1: Omics studies on the emerging MERS coronavirus and the coronavirome of mid-Atlantic bats Project Leader (PL): Frieman, M. DESCRIPTION (provided by applicant): Emerging viruses represent a significant public health threat around the world. The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently emerged Middle East Respiratory Syndrome Coronavirus (MERS-CoV) represent two of an increasing number of emergent viruses that can and have caused lethal disease around the world. It is critical that we understand the underlying biological basis of thei increased pathogenesis in animals and humans. It has also becoming recognized that most recently emerged highly pathogenic viruses have origins in bats. Bats are found on every continent and number over 1100 species in total. The interconnected bat ecosystem provides a diverse and unending supply of novel viruses and niches that harbor hundreds of viruses never before identified. To better characterize the recently emerged MERS-CoV we will use large-scale genomic approaches to uncover the host/pathogen interactions of MERS-CoV with the host. Using highly specialized genomics approaches we will also identify novel viruses in bats caught in Maryland with a focus on the characterization of novel Coronaviruses. Together with the state-of-the-art computational biology and technology Core, the PI of Project 1 will characterize and identify mechanisms of pathogenesis for emerging and yet to emerge viral pathogens. RELEVANCE: The emergence of SARS-CoV in 2003 and the recent emergence of MERS-CoV in 2012 from bats highlight the need to understand the pathogenesis of these viruses and the identification of other potential Coronaviruses in bats. The proposed research in this project will identify the mechanism of pathogenesis for these viruses and produce novel compounds that will lead to therapeutic treatments for these infections.