Hsien Wu and Daisy Yen Wu Professor of Biological Chemistry and Molecular Pharmacology, Program Co-director
240 Longwood Ave.
Boston, MA 02115
Lab Size: Between 10 and 12
The laboratory studies how naturally occurring small molecules, especially those from bacteria, control biological processes. Organizing themes include: 1) function-based discovery of microbially-produced small molecules and their roles in multilateral symbioses, 2) function-based discovery of biologically active small molecules controlling eukaryotic development, 3) genome-based discovery of bacterially-produced small molecules. The laboratory is also involved in infectious disease research especially alternative approaches to treating bacterial and fungal infections.
1. In the past few years, we have focused on multilateral symbioses involving bacteria, partly because they are widespread and interesting 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-farming ants, bark beetles, termites, and most recently social amoebas.
2. We also continue to discover small molecules in a more medically relevant context: how bacterially produced small molecules regulate eukaryotic evolution, development, and immune responses.
3. In the past few years, it has become quite clear that well studied bacteria – including the producers of drugs that are used on the ton scale – are genetically capable of producing many more potentially useful small molecules. The biosynthetic genes can be identified in sequenced genomes but the associated molecules have never been characterized. We are working on several approaches to discovering these cryptic metabolites.
A bacterial symbiont is converted from an inedible producer of beneficial molecules into food by a single mutation in the gacA gene. Stallforth P, Brock DA, Cantley AM, Tian X, Queller DC, Strassman JE, Clardy J. Proc. Natl. Acad. Sci. USA 2013,
Synthesis and activity of biomimetic biofilm disruptors. Böttcher T, Kolodkin-Gal, Kolter R, Losick R, Clardy J. J. Am. Chem. Soc. 2013, 135;2927-2930.
A bacterial sulfonolipid triggers multicellular development in the closest living relatives of animals. Alegado RA, Brown LW, Cao S, Dermenjian RK, Zuzow R, Fairclough SR, Clardy, J, King N. eLife 2012, 1:e00013.
Mixing and matching siderophore clusters: structure and biosynthesis of serratiochelins from Serratia sp. V4. Seyedsayamdost MR, Cleto S, Carr G, Vlamakis H, Joao Veira M, Clardy J. J. Am. Chem. Soc. 2012, 134:13550-13553.
Small molecule perimeter defense in entomopathogenic bacteria. Crawford JM, Portmann C, Zhang X, Roeffaers MB, Clardy J. Proc. Natl. Acad. Sci. USA 2013, 109:10821-10826.