Research interests and projects
My interests are in the chemical analysis of biological and environmental samples to study the chemical response of micro-organisms to environmental stress. In particular, I have been developing and applying methods for trace metal analysis and speciation. In my current project, I make use of metabolomics approaches for discovery, identification, and quantification of siderophores and other metallophores. I work in an interdisciplinary group, lead by François M. M. Morel, dedicated to studying the impact of trace-metal availability on molecular processes and global biogeochemical cycles (http://morel.princeton.edu/).
Role of essential trace-metals in biology and environment
Transition metals are required in a major fraction of proteins and other bio-molecules. They function as catalytic centers or to give molecular structure. In the oceans and even in some terrestrial environments, Fe, Zn, Co, Mn, and other transition metals are present at trace concentrations that can limit the growth of micro-organisms and determine the cycles of the main elements of life.
While being present at trace concentrations, speciation experiments show that these metals are frequently bound to organic ligands which determine their biological availability. There is a feedback between micro-organisms which can produce these ligands, often in response to low metal concentrations, and cycling of trace metals. Strong ligands for iron (siderophores) and other metals (metallophores) can be released by bacteria and play an important role not only in the environment but also in bacterial interactions and pathogenicity of bacteria.
Siderophore metabolomics and identification of metal chelating compounds
The presence and biological significance of organic ligands that bind iron and other trace-metals in environmental and biological samples has been well established over the last decades through speciation experiments using electrochemistry and other techniques. However, the chemical identity of these compounds is often unknown due to low concentrations and complex samples. I have developed and applied liquid chromatography mass spectrometry (LC-MS) based approaches to harness the sensitivity and resolution of modern LC-MS instrumentation for structural characterization and quantification of unknown metal chelating compounds in bacterial cultures and environmental samples.
|Workflow for discovery and identification or characterization of known or unknown siderophores and other metallophores by high-resolution LC-MS|
Recent results - A study of the siderophore metabolome of N2-fixing bacteria
Application of the new approaches for a study of Fe chelating ligands produced by ubiquitous N2 fixing Azotobacters revealed a large number of siderophore structures that fell into few major siderophore families, each comprising of a set of structural analogs and corresponding to separate biosynthetic gene clusters. Systematic analysis of LC-MS/MS data allowed the identification of many new compounds as analogs of previously described siderophore structures. In addition, isolation and structural characterization by NMR and other techniques revealed a new siderophore type with an unusual Fe coordination chemistry. Despite differences in siderophore structures produced by different Azotobacter species and strains, common patterns in response to Fe availability were observed. These studies provide new tools for the characterization of an important group of secondary metabolites produced by bacteria and other micro-organisms and reveal new insight into the strategies of bacteria for Fe chelation and acquisition.