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
Unequivocal determination of complex molecular structures using anisotropic NMR measurements.
Authors: Authors: Liu Y, Saurí J, Mevers E, Peczuh MW, Hiemstra H, Clardy J, Martin GE, Williamson RT.
Science
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Linear Peptides Are the Major Products of a Biosynthetic Pathway That Encodes for Cyclic Depsipeptides.
Authors: Authors: Wyche TP, Ruzzini AC, Beemelmanns C, Kim KH, Klassen JL, Cao S, Poulsen M, Bugni TS, Currie CR, Clardy J.
Org Lett
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Macrotermycins A-D, Glycosylated Macrolactams from a Termite-Associated Amycolatopsis sp. M39.
Authors: Authors: Beemelmanns C, Ramadhar TR, Kim KH, Klassen JL, Cao S, Wyche TP, Hou Y, Poulsen M, Bugni TS, Currie CR, Clardy J.
Org Lett
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Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases.
Authors: Authors: Guo CJ, Chang FY, Wyche TP, Backus KM, Acker TM, Funabashi M, Taketani M, Donia MS, Nayfach S, Pollard KS, Craik CS, Cravatt BF, Clardy J, Voigt CA, Fischbach MA.
Cell
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Chemical warfare: The battle between termite-associated actinobacteria and Trichoderma harzianum, a fungal pathogen.
Authors: Authors: Mevers E, Saurí J, Moser A, Varlan M, Martin GE, Clardy JC.
Planta Med
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A common bacterial metabolite elicits prion-based bypass of glucose repression.
Authors: Authors: Garcia DM, Dietrich D, Clardy J, Jarosz DF.
Elife
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Dynamic metabolic exchange governs a marine algal-bacterial interaction.
Authors: Authors: Segev E, Wyche TP, Kim KH, Petersen J, Ellebrandt C, Vlamakis H, Barteneva N, Paulson JN, Chai L, Clardy J, Kolter R.
Elife
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Selvamicin, an atypical antifungal polyene from two alternative genomic contexts.
Authors: Authors: Van Arnam EB, Ruzzini AC, Sit CS, Horn H, Pinto-Tomás AA, Currie CR, Clardy J.
Proc Natl Acad Sci U S A
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Compounds that select against the tetracycline-resistance efflux pump.
Authors: Authors: Stone LK, Baym M, Lieberman TD, Chait R, Clardy J, Kishony R.
Nat Chem Biol
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Diversity-oriented synthesis yields novel multistage antimalarial inhibitors.
Authors: Authors: Kato N, Comer E, Sakata-Kato T, Sharma A, Sharma M, Maetani M, Bastien J, Brancucci NM, Bittker JA, Corey V, Clarke D, Derbyshire ER, Dornan GL, Duffy S, Eckley S, Itoe MA, Koolen KM, Lewis TA, Lui PS, Lukens AK, Lund E, March S, Meibalan E, Meier BC, McPhail JA, Mitasev B, Moss EL, Sayes M, Van Gessel Y, Wawer MJ, Yoshinaga T, Zeeman AM, Avery VM, Bhatia SN, Burke JE, Catteruccia F, Clardy JC, Clemons PA, Dechering KJ, Duvall JR, Foley MA, Gusovsky F, Kocken CH, Marti M, Morningstar ML, Munoz B, Neafsey DE, Sharma A, Winzeler EA, Wirth DF, Scherer CA, Schreiber SL.
Nature
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