Saturday, April 12, 2008

Last Day: Liveblogging the Molecular Evolution/Infectious Diseases Keystone Conference

Day 3
Eun-Chung Park (NIAID) made an announcement about NIH funding opportunities for non-US investigators. There is a new PA for international research in infectious diseases PAR-08-130.

Morning Session
David Alland (UMDNJ) gave a fantastic talk on the evolution of drug resistance in M. tuberculosis. He uses SNP-based phylogenetic analysis to link specific mutations to drug resistance phenotypes. In the setting of confusing data as to which mutations actually cause resistance and which are simply epidemiologically linked, he showed that phylogenetic analyses can provide answers, including answers that impact patient care, that other techniques cannot.

M. Cristina Gutierrez spoke about “rethinking tuberculosis in the light of evolution.” She focused on smooth-colony variants of Mycobacterium tuberculosis (MTb), which are an uncommon but confusing cause of human disease. Using MLST, she showed that MTb can be divided into distinct lineages, which she calls MTb and Mycobacterium prototuberculosis. She provided estimates of the age of the split between the two lineages and hypothesized about the relevance of this to TB in hominid ancestors.

Bruce Levin delivered an “opinionated rant” about recombination in bacteria with a focus on transformation. Using a combination of equations, experiments, and “yak-yak,” he put forward a new hypothesis about the evolution of transformation and genetic competence. He hypothesizes that although competent bacteria may have a growth deficit in comparison to non-competent competitors, in the setting of occasional, punctuated selective pressure, the competent strains will predominate.

A short talk describing MLST analysis was given by Sebastien Gagneux from MRC. He focuses on the biogeography of MTb and links phylogenetic analysis to hypotheses about human migrations.

Anne Buboltz from Penn State gave a short talk about a strain of Bordetella bronchiseptica that has become less virulent due to a recombination event. Her group mapped this recombination, and using careful genetic studies linked the genes involved to the loss of virulence.

In the afternoon session, Jim Musser gave a phenomenal talk about his group’s integrated systems biology approach to group A streptococcus virulence. Using longitudinally collected human disease isolates, full genome sequencing, and unique animal models, they have linked single mutations on the streptococcal chromosome (including a single nucleotide change in one case) to both overall virulence and (in at least one case) to anatomic site specificity. Amazing, amazing work. I plan to go back and read several of the papers that he described again.

Nancy Moran gave an exciting talk about the evolutionary genomics of bacterial symbionts of insects. This is an area that has exploded recently, especially with the publication of the paper taking a genomic look at the dual sharpshooter symbiosis. She gave an overview of the field, focusing on the common characteristics of genomes of obligate symbionts (small size, loss of metabolic functions), the importance of maternal passage of symbionts to their evolution, and how more recently established symbioses may differ from ancient ones.

Mark Achtman (University College Cork) spoke about the complex and intimate relationship between Helicobacter pylori and humans. In addition to learning a tremendous amount about the organism itself, his group has used the rapid evolution and recombination within H. pylori to trace human migrations at a level of resolution that human genomic studies cannot approach. This is an extremely useful and creative use of evolutionary and phylogenetic analysis and a field that is just beginning.

Martin Antonio spoke about Streptococcus pneumoniae, an extremely important cause of childhood mortality worldwide. His group looked at invasive S. pneumoniae disease in Africa and, through a detailed MLST analysis, linked a specific serotype to severity of disease.

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