Picture of Jon Clardy

Jon Clardy, Ph.D.

Christopher T. Walsh Professor of Biological Chemistry and Molecular Pharmacology

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes. 

Research:

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes.  Organizing themes include: 1) function-based discovery of microbially-produced small molecules and their roles in microbial symbioses , 2) function-based discovery of biologically active small molecules using high-throughput screening,  3) genome-based discovery of bacterially-produced small molecules. 

1.  We have focused on the small molecule exchanges that underlie multilateral symbioses involving bacteria, partly because they are widespread and poorly understood and partly because they lead to the discovery of new useful molecules in the biological context in which they evolved.  Current projects involve the bacterial symbionts of fungus-growing ants, members of the human gut microbiome linked to disease, and interactions between micro-algae and bacteria.

2.  We also continue to discover small molecules in a more medically relevant context: high-throughput screening for a variety of diseases.  In these projects we have focused on antibacterial, antifungal, and antiparasitic agents along with immunomodulators and anticancer agents. 

3.  It is now quite clear that well studied bacteria – the producers of drugs that are used on the ton scale, for example – are genetically capable of producing many more potentially useful small molecules.  The biosynthetic gene can be seen but the associated molecules have never been characterized.  Ways to access these cryptic metabolites is a current focus of the laboratory.

Address: 

Room C-643

240 Longwood Avenue

Boston, MA 02115

Publications View
Synthetic libraries of tyrosine-derived bacterial metabolites.
Authors: Authors: Georgiades SN, Clardy J.
Bioorg Med Chem Lett
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Citral sensing by Transient [corrected] receptor potential channels in dorsal root ganglion neurons.
Authors: Authors: Stotz SC, Vriens J, Martyn D, Clardy J, Clapham DE.
PLoS One
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Development of a fluorescence polarization based assay for histone deacetylase ligand discovery.
Authors: Authors: Mazitschek R, Patel V, Wirth DF, Clardy J.
Bioorg Med Chem Lett
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The evolution of gene collectives: How natural selection drives chemical innovation.
Authors: Authors: Fischbach MA, Walsh CT, Clardy J.
Proc Natl Acad Sci U S A
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High-throughput screens for small-molecule inhibitors of Pseudomonas aeruginosa biofilm development.
Authors: Authors: Junker LM, Clardy J.
Antimicrob Agents Chemother
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Detecting binding interactions using microarrays of natural product extracts.
Authors: Authors: Schmitz K, Haggarty SJ, McPherson OM, Clardy J, Koehler AN.
J Am Chem Soc
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Cyclic AMP directly activates NasP, an N-acyl amino acid antibiotic biosynthetic enzyme cloned from an uncultured beta-proteobacterium.
Authors: Authors: Clardy J, Brady SF.
J Bacteriol
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Bombyx mori pheromone-binding protein binding nonpheromone ligands: implications for pheromone recognition.
Authors: Authors: Lautenschlager C, Leal WS, Clardy J.
Structure
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One pathway, many products.
Authors: Authors: Fischbach MA, Clardy J.
Nat Chem Biol
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Small-molecule pheromones that control dauer development in Caenorhabditis elegans.
Authors: Authors: Butcher RA, Fujita M, Schroeder FC, Clardy J.
Nat Chem Biol
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