Our research is directed at characterizing structures and biological functions of biogenic small molecules (BSM’s). BSM’s play important roles in most biological processes, and detailed knowledge of their chemical structures and their interactions with other biomolecules is essential for advancing our molecular understanding of life. BSM’s regulate development and immune responses in plants and animals, and serve important functions in interactions of different organisms with each other. As a result, an organism's metabolome essentially comprises a collection of small molecules with potentially useful affinities for specific molecular targets. Not surprisingly, BSM’s constitute the most important source of lead structures for drug development.
Compared to template-derived biological macromolecules such as proteins and nucleic acids, BSM’s are chemically much more diverse and correspondingly present great analytical challenges. As a result, genomic and proteomic knowledge has not yet been complemented by a comprehensive characterization of structures and functions of metabolomes, presenting one of the most significant barriers toward advancing our understanding of biological pathways.
The Schroeder lab aims to help close this knowledge gap by developing approaches for a more systematic structural and functional characterization of BSM’s. Usually, BSM’s occur as - often minor - components of a more or less complex biological matrix, comprising a large number of BSM's and other biomolecules. Traditional approaches for the characterization of BSM's such as HPLC-MS or activity-guided fractionation have distinct disadvantages that severely limit their applicability. Our aims is to develop NMR spectroscopy-based approaches that complement or enhance traditional methodology by enabling detailed characterization of BSM’s in complex biological samples, with regard to both chemical structure and biological function.
Based on NMR-spectroscopic methodology we have engaged in a comprehensive effort to characterize structures and functions of the metabolome (the entirety of all BSM’s) produced by the model organism Caenorhabditis elegans, focusing on several newly discovered compounds that control development, and ultimately lifespan. In addition we have started a project directed at investigating the chemical ecology of microorganisms in search of leads for new antibiotics. Complementing our interests in analytical chemistry, we pursue development of efficient syntheses for newly identified compounds with particular biological significance.
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The relevance of nucleic acids, proteins, and carbohydrates for all aspects of biology is well established, but the varied and often unexpected roles of so-called “secondary”metabolites are just now being discovered. Secondary metabolites regulate development and immune responses in plants and animals (such as hormones) and also play an important role in the interactions of different organisms with each other. Identifying secondary metabolites and determining their function is an important area of biomedical research that can help scientists better understand diseases such as bacterial infections, diabetes and cancer, as well as the phenomenon of aging.
Secondary metabolites are very different from proteins and nucleic acids. They constitute a chemically diverse class of compounds,which have so far resisted systematic analysis. Frank Schroeder’s laboratory is developing new analytical methodology based on a technique called NMR spectroscopy,which promises to greatly simplify scientists’ ability to identify the chemical structure of these compounds and find their biological functions. Using this approach, Schroeder’s team is investigating the role of secondary metabolites in specific aspects of plant and animal biology.
In one area of research, Schroeder is investigating secondary metabolites produced by the nematode Caenorhabditis elegans. Nematodes are roundworms that are about 1 mm in length and ubiquitous in the soil. Scientists believe that many of the physiological pathways in C. elegans are analogous to corresponding pathways in higher animals, and as a result, nematodes have become an important model system for human disease and aging. Although the entire C. elegans genome – about 20,000 genes – was sequenced more than 10 years ago, little is known about its secondary “metabolome.” Recently, Schroeder’s group identified several new compounds that influence mating behavior, as well as pathways involved in nematode development and life span regulation. The ultimate goal of this research is to identify the entire C. elegans secondary metabolome for chemical structure and biological function.
In other research, Schroeder and colleagues recently used his NMR-spectroscopic approach to identify a previously unknown human hormone that controls the excretion of sodium via the kidneys. This discovery may one day lead to a new approach for treating high blood pressure.
