My research group seeks to understand communication and compatibility between bacteria and eukaryotic host organisms, with an emphasis on plant-associated microbes. We also study natural variation in bacterial gene essentiality, with a goal to understand how the essentiality of particular genes is dictated by genomic context. We are also developing new methods for antibiotic discovery that capitalize on massively parallel DNA sequencing and computational analysis.
One project concerns the chemical dialogue between the nitrogen-fixing bacterium Sinorhizobium meliloti and legume hosts of the genus Medicago. We are learning that legume cells produce symbiosis-inducing peptides that drive bacteria into a symbiotic state; however, the bacteria may be less responsive to these peptide signals (and therefore less symbiotically compatible) due to plasmid-encoded compatibility factors that are under active investigation. Our current models emphasize active peptide degradation and differential peptide uptake as primary mechanisms.
A second project is focused on identifying essential genes in bacteria, using massively parallel transposon insertion sequencing. We are interested in which genes are essential for viability, which genes are conditionally essential depending on environmental or genomic context, and we are developing high-resolution technologies for investigating how essential genes may be truncated or split apart while still allowing functionality.
A third project is focused on antibiotic synthesis and mechanism of action. In one facet of this study we are trying to understand the synthesis of thiopeptide antibiotics, with the aim of using this natural pathway as a template for developing new antimicrobial compounds. In a second facet of the project we are developing powerful methods for screening through millions of peptide-based molecules for novel antibiotics.
