Jon Clardy

Department of Biological Chemistry and Molecular Pharmacology
Harvard Medical School
Building C, 6th Floor, C-643
240 Longwood Ave.
Boston, MA 02115
Tel: (617) 432-2845
Fax: (617) 432-6424
Email: jon_clardy@hms.harvard.edu
Web Page:The Clardy Lab Page
8 postdoctoral fellows, 4 graduate students

The laboratory focuses on biologically active small molecules, especially those found in nature, and their interactions with their cellular targets with an overall goal of understanding how small molecules control biological processes. Projects can be roughly divided into three groups: 1) biologically active small molecules from natural sources arising from (drug) discovery-based assays, 2) small molecules that function as carriers of biological information, and 3) discovery of biologically active small molecules using ecologically- and physiologically-based approaches

1. We use a variety of biological assays, including high throughput screening, to discover biologically active small molecules, especially potential drug candidates.  Several current projects involve finding new small molecules from biodiverse regions – Costa Rica and Madagascar – using high-throughput screening and secondary assays against a variety of biological targets.  The assays in these screens increasingly reflect the growing interest in infectious diseases.

2. The laboratory also studies biologically active small molecules in their natural, as opposed to therapeutic, context, and the small molecules that serve as biological information carriers are of special interest. Some current projects involve signaling systems in C. elegans such as the dauer and alarm pheromones, the chemical ecology of interactions between different organisms such as insects and bacteria, virulence factors and other small molecule controlled behaviors.

3. The laboratory is exploiting ways to capture the biologically active small molecules made by so-called cryptic bacterial pathways with both functional and bioinformatic approaches. A variety of individual projects, especially those involving the antibiotics from actinomycetes and other bacteria are being pursued.

References:

• Baniecki, ML, Wirth, DF, and Clardy, J,  A high-throughput Plasmodium falciparum growth assay for malaria drug discovery, Antimicrob. Agents Chemother. 2007, 51, 716-723.
• Butcher, RA, Fujita, M, Schroeder, FC, and Clardy J, Small-molecule pheromones that control dauer development in Caenorhabditis elegans, Nature Chem. Biol. 2007, 3, 421-422.
• Butcher, RA, Schroeder, FC, Fischbach, MA, Straight, P, Kolter, R, Walsh, CT, and Clardy, J, The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis, Proc. Natl. Acad. Sci. USA 2007, 104, 1506-1509.
• Fischbach, MA, Walsh, CT, Clardy J The evolution of gene collectives: How natural selection drives chemical innovation, Proc. Natl. Acad. Sci. USA 2008, 105, 4601-4608.