“Coaxing drugs from gifted bugs.”
Streptomyces bacteria and their close relatives rank amongst the most prolific producers of small molecules known to science. These organisms produce nearly half of all known microbial bioactive natural products and nearly 2/3rds of our clinically- utilized antibiotics. Understandably, they’ve had an immense impact on medicine and agriculture as producers of human and animal therapeutics, molecular probes, and crop protective agents.
Although these bacteria have been a traditional source of valuable molecules, more recent genome analyses indicate that only a small fraction of their biosynthetic potential has been tapped thus far. This realization has engendered a new research paradigm; that of sequencing-based molecule discovery. Cognizant of the true molecule production capacity of these organisms, we’re now enabled to begin deciphering the evolutionary roles of these chemical modulators while creating opportunities to discover novel pharmacophores.
The Blodgett lab is interested in a number of interdisciplinary questions surrounding bacterial small molecule production. These inquiries broadly span the fields of biology, chemistry and ecology.
-How do Streptomycetes interact with their surroundings using small molecules?
(Chemical Ecology)
-How are certain bioactive molecules produced?
(Biosynthesis, Regulation & Metabolism)
-How can we manipulate producing organisms to increase production yields and boost molecule discovery rates?(Bioengineering and Synthetic Biology)
– Can we combine knowledge gleaned from answering the questions above into insightful new ways of discovering potentially useful molecules?
(Drug and Agricultural lead Discovery)
To investigate these questions, we use a mix of traditional and modern approaches. Biological techniques include microbial isolation, genetic engineering, fermentation, regulatory analyses, comparative genomics, and enzymology. These lines of study, combined with chemical analyses performed both in this lab and with collaborators, aim to enable a broader understanding of the “Hows and Whys” of bacterial secondary metabolism.