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. The laboratory is also involved in infectious disease research and current projects include developing a high-throughput screen for small molecules that influence the liver stage of malaria.
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, insect-killing nematodes, bark beetles, and microalgae.
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 global infectious disease and microbially produced small molecules from tropical environments. This interest has led to the development of several high-throughput screens for antimalarial small molecules.
3. In the past few years, it has become 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.
Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis. Oh, D.C., Poulsen, M., Currie, C.R., & Clardy J. Nat. Chem. Biol. 2009, 5, 391-3.
Discovery of 3-formyl-tyrosine metabolites from Pseudoalteromonas tunicata through heterologous expression. Blasiak, L.C. & Clardy, J. J. Am. Chem. Soc. 2010, 132, 926-7.
Regulating alternative lifestyles in entomopathogenic bacteria. Crawford, J.M., Kontnik, R., & Clardy, J. Curr. Biol. 2010, 20, 69-74.