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Frank C. Schroeder

Associate Professor

Boyce Thompson Institute, Room 425
schroeder@cornell.edu
607-254-4391

Website(s)

Overview

>>Please see our Group Website for recent news and publications, research updates, and teaching

Our research is dedicated to develop new strategies for a high-throughput structural and functional annotation of biogenic small molecules, combining expertise in molecular biology, bioinformatics, and analytical chemistry. Biogenic small molecules (BSMs) play important roles in most biological processes and represent the most important source for new drug leads, especially for the treatment of infectious disease and cancer. Detailed knowledge of small-molecule structures, their biosyntheses, and their interactions with other biomolecules is essential for advancing drug development as well as for the understanding of disease-relevant interactions of microorganisms with their human, animal, or plant hosts. The lab currently focuses on two major projects:

1. Based on combining NMR-spectroscopic methodology with genetic approaches, we have engaged in a comprehensive effort to characterize structures and functions of the metabolome (the entirety of all BSMs) produced by the model organism Caenorhabditis elegans, focusing on several newly discovered compounds that control development, aging, and several social behaviors. Our research has led to the identification of several 100 new BSMs in C. elegans and other nematodes, including parasitic species. These new metabolites are derived from modular assembly of building blocks from all major metabolic pathways, presenting a new paradigm of small molecule biosynthesis in metazoans. Many of these compounds have entirely unexpected structures and biological activities, and current efforts in my lab focus on the elucidation of the biosynthesis of these compounds and their role in regulating conserved endocrine signaling.

2. Complementing our work on nematodes, we apply 2D NMR-based comparative metabolomics as a new strategy to identify the small-molecule products of cryptic PKS and NRPS gene clusters in bacteria and fungi, focusing in particular on the identification of virulence factors and antimicrobial compounds. BSMs of microbial origin represent the most important source for new drug leads, especially for the treatment of infectious disease and cancer. Recent technical advances that further accelerate detection and characterization of new structural entities include the development of algorithms for the partially automated comparative analysis of high-resolution 2D NMR spectra and the use of heterologous expression of gene clusters in A. nidulans.

As a necessary component of our chemical biology-oriented research, we develop novel strategies for the syntheses of newly identified compounds with particular structural or biological significance.

Keywords

Chemical Biology Metabolomics Synthesis Bioorganic Chemistry

Departments/Programs

  • Chemistry and Chemical Biology

Graduate Fields

  • Biochemistry, Molecular and Cell Biology
  • Chemistry and Chemical Biology
  • Computational Biology

Research

>>Please see our Group Website for recent news and publications, research updates, and teaching

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.

Please visit our research pages for more details!

Courses