Cold Spring Harbor Laboratory Courses in Phage and Bacterial Genetics: A Catalyst for Innovation in Molecular Biology, Genetics, and Microbiology.

The ability to answer complex scientific questions depends on the experimental methods available. New methods often allow scientists to answer questions that were previously intractable, leading to discoveries that often dramatically change a field. Beginning with Max Delbrück's famous summer phage course at Cold Spring Harbor Laboratory in 1945, the Phage, Bacterial Genetics, and Advanced Bacterial Genetics courses have provided hands-on experiences to generations of scientists that facilitated the broad adoption of new experimental methods into laboratories around the world. These methods have led to discoveries that changed the way we think about genetics, bacteria, and viruses, transforming our understanding of biology. The impact of these courses has been further amplified by published laboratory manuals that provide detailed protocols for the evolving experimental toolkit. These courses catalyzed intensive and critical discourse about ideas that were previously intractable and provided novel experimental approaches to answer new questions-a process that epitomizes Thomas Kuhn's concepts of Scientific Revolution, spinning off the new field of Molecular Biology and dramatically changing the field of microbiology.

Genomic Comparison of the Closely-Related Salmonella enterica Serovars Enteritidis, Dublin and Gallinarum.

The Salmonella enterica serovars Enteritidis, Dublin, and Gallinarum are closely related but differ in virulence and host range. To identify the genetic elements responsible for these differences and to better understand how these serovars are evolving, we sequenced the genomes of Enteritidis strain LK5 and Dublin strain SARB12 and compared these genomes to the publicly available Enteritidis P125109, Dublin CT 02021853 and Dublin SD3246 genome sequences. We also compared the publicly available Gallinarum genome sequences from biotype Gallinarum 287/91 and Pullorum RKS5078. Using bioinformatic approaches, we identified single nucleotide polymorphisms, insertions, deletions, and differences in prophage and pseudogene content between strains belonging to the same serovar. Through our analysis we also identified several prophage cargo genes and pseudogenes that affect virulence and may contribute to a host-specific, systemic lifestyle. These results strongly argue that the Enteritidis, Dublin and Gallinarum serovars of Salmonella enterica evolve by acquiring new genes through horizontal gene transfer, followed by the formation of pseudogenes. The loss of genes necessary for a gastrointestinal lifestyle ultimately leads to a systemic lifestyle and niche exclusion in the host-specific serovars.

Genomic and Metagenomic Approaches for Predicting Pathogen Evolution.

Global climate change can alter the distribution of microbial pathogens and vectors that transmit infectious diseases, exposing humans to newly emerging or reemerging diseases. Early detection of potential pathogens and vectors in the environment can facilitate upstream interventions that limit the spread of infectious disease. Metagenomics is the analysis of DNA sequences from a population of microorganisms in a particular environment, followed by the computational reconstruction of the data to determine what organisms are present and predict their role in the environment. Defining the microbial populations associated with humans, animals, and their environment provides insight into the structure of microbial communities in any particular niche, including the abundance, diversity, and composition of the microbes and viruses present. It can also reveal the distribution of virulence genes within that niche. These data can be used to identify reservoirs of pathogens in an environment and predict environments with a high probability for evolution of new pathogens or outbreaks caused by known pathogens, thereby facilitating approaches to prevent infections of animals or humans before serious outbreaks of infectious disease.