Rob DeSalle - US grants

DESCRIPTION (provided by applicant): It is widely acknowledged that the acquisition of foreign DNA elements by Bacteria has contributed significantly to the emergence of new pathogens. Indeed, horizontal transfer of is believed to be an important process in the evolution of many microorganisms. Transferred genes can provide traits that confer a selective advantage to pathogens and confer virulence on non-pathogens. Genes for antibiotic resistance, toxin production, and host-specificity can all be acquired horizontally. Though much is understood about the mechanical processes of horizontal transfer in bacterial model systems, less is known about the historical dynamics of horizontal transfer and its impact on the phenotype and genomes of host organisms. Phylogenetic analysis offers a powerful framework to identify horizontal transfer and test hypotheses about its evolutionary dynamics and implications. We propose to adapt existing phylogenetic techniques and develop new ones to investigate at high resolution the process of horizontal transfer and its impact on the evolution of infectious disease. We also propose to use molecular genetic methods in the laboratory to test phylogeny-based predictions about horizontal transfer. To analyze gene transfer, it is critical to examine a system that can be horizontally acquired, is widely distributed, and allows for dense taxon sampling. The highly conserved Widespread Colonization Island (WCI) presents an unparalleled model system to test hypotheses and develop methodologies to better understand horizontal transfer. The WCI, first identified in the periodontal pathogen Actinobacillus actinomycetemcomitans, contains genes essential for the tenacious, nonspecific adherence of the bacterium to surfaces, and fibril biogenesis. Sequence analysis shows that the WCI is distributed in a wide array of pathogens and nonpathogens that inhabit very distinct niches. Preliminary phylogenetic analyses and other evidence suggest that the WCI has experienced multiple horizontal transfer events. The WCI will be used as a model system to study the process of horizontal transfer. Our objectives are: (1) to test and develop methods that can reliably identify historical transfer events, the donor and recipient lineages involved, and the relative dates of their occurrence; (2) to develop phylogenetic techniques and methods for genome analysis to understand the emergence of pathogenicity due to horizontal transfer; (3) to understand the co-evolution of the components of a genetic island with each other and with their bacterial host(s); (4) to identify genetic or phylogenetic barriers to the transfer of pathogenicity islands among hosts and; (5) to design accessible, computer-based phylogenetic and genomic methods for the analysis of horizontal transfer and host/parasite co-evolution. The WCI system offers an outstanding opportunity to understand horizontal transfer on a large scale and to develop new methodologies that can be generalized for the analysis of horizontal transfer, infectious disease, and the evolution of virulence in other systems.

DESCRIPTION (provided by applicant): The American Museum of Natural History (AMNH) requests SEPA support for the five-year project, Human Health, Biodiversity, and Microbial Ecology: Strategies to Educate. The project's overarching goal is to promote public awareness and deepen understanding of the critical impact of biodiversity on human health, with specific attention to the human microbiome and how the diversity of nature's innovations - chemical, anatomical, and physiological - are of critical value to biomedical research. The three specific aims to achieve this goal are: (1) spotlight emerging research at the intersection of biodiversity and human health by providing the general public, students, and teachers with engaging opportunities to interact with experts in the field, learn about this critical topic in AMNH's hall, and deepen their understanding through resources that extend beyond AMNH's walls; (2) provide information to the public and science cultural institutions that will lead to a better understanding of audiences' specific interests, levels of understanding, and gaps in knowledge concerning the connections between biodiversity and human health; and (3) contribute critical insights about the design of learning experiences and resources effective in engaging and educating diverse audiences about the relevance of biodiversity to human well-being, and giving them the tools to increase their understanding of this topic. Specific project components include: a SEPA exhibition element in AMNH's upcoming exhibit on poison; a smartphone application tour of AMNH permanent exhibition halls through the lens of biodiversity and human health; a series of Conversations with Experts for adults, students, and teachers, based on the Science Cafe format; Museum visitor polling that will contribute to a gap analysis of public knowledge of the topic of biodiversity and human health; and online resources and dissemination. External evaluation will help assess the value of all components in increasing public understanding of biodiversity and human health topics, as well as provide information to be shared with other informal science institutions. As a leading scientific research and education institution, AMNH is well prepared to use its own expertise in educational programming and exhibitions, as well as its research capacity in comparative and molecular biology, phylogenetics, and biodiversity science, to work with participating NIH scientists to translate and disseminate the work of NIH and other researchers to broad online and on-site audiences.