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
Common biosynthetic origins for polycyclic tetramate macrolactams from phylogenetically diverse bacteria.
Authors: Authors: Blodgett JA, Oh DC, Cao S, Currie CR, Kolter R, Clardy J.
Proc Natl Acad Sci U S A
View full abstract on Pubmed
D-amino acids trigger biofilm disassembly.
Authors: Authors: Kolodkin-Gal I, Romero D, Cao S, Clardy J, Kolter R, Losick R.
Science
View full abstract on Pubmed
Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases.
Authors: Authors: Dawlaty J, Zhang X, Fischbach MA, Clardy J.
J Nat Prod
View full abstract on Pubmed
Siderophores from neighboring organisms promote the growth of uncultured bacteria.
Authors: Authors: D'Onofrio A, Crawford JM, Stewart EJ, Witt K, Gavrish E, Epstein S, Clardy J, Lewis K.
Chem Biol
View full abstract on Pubmed
Chemical modification of the insecticidal briantheins X and Y.
Authors: Authors: Cronan JM, Lee A, Liang J, Clardy J, Cardellina JH.
J Nat Prod
View full abstract on Pubmed
Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264.
Authors: Authors: Seyedsayamdost MR, Chandler JR, Blodgett JA, Lima PS, Duerkop BA, Oinuma K, Greenberg EP, Clardy J.
Org Lett
View full abstract on Pubmed
A non-radioactive DAPI-based high-throughput in vitro assay to assess Plasmodium falciparum responsiveness to antimalarials--increased sensitivity of P. falciparum to chloroquine in Senegal.
Authors: Authors: Ndiaye D, Patel V, Demas A, LeRoux M, Ndir O, Mboup S, Clardy J, Lakshmanan V, Daily JP, Wirth DF.
Am J Trop Med Hyg
View full abstract on Pubmed
Discovery of 3-formyl-tyrosine metabolites from Pseudoalteromonas tunicata through heterologous expression.
Authors: Authors: Blasiak LC, Clardy J.
J Am Chem Soc
View full abstract on Pubmed
Regulating alternative lifestyles in entomopathogenic bacteria.
Authors: Authors: Crawford JM, Kontnik R, Clardy J.
Curr Biol
View full abstract on Pubmed
Antiplasmodial activity of piperazine sulfonamides.
Authors: Authors: Martyn DC, Cortese JF, Tyndall E, Dick J, Mazitschek R, Munoz B, Clardy J.
Bioorg Med Chem Lett
View full abstract on Pubmed