Research: Back in the Lab
Scientists have been characterizing and testing the drug-like molecules biosynthesized by microorganisms for years with many of the drugs on the market today originating from this process. The hunt for new drugs in the Sherman lab begins with collection of sediments and sponges from all over the world. The sediments collected in the May 2005 expedition to Papua New Guinea were carefully packed away, shipped (with official export permits from the PNG government) and are now ready to begin the research journey to potentially new medicines.
Back in his lab in the United States, Professor David Sherman turns over the 1500+ samples to laboratory supervisor, Pam Schultz. Pam has run nearly 1000 cultures on core samples of sand and mud collected from previous expeditions to the ocean bottoms of places like Papua New Guinea, Panama, and the U.S. Virgin Islands.
The sediments collected are full of bacterial cells and presumably spores which when placed on Petri dishes under carefully monitored conditions will tease out the bacteria (actinomycetes species, note the ring pattern). It takes two weeks to several months for the microbes of interest to appear. These new bacteria are phylogenetically characterized using 16S rRNA gene sequence analysis, cell wall composition and fatty acid analysis, menaquinone characterization and genome fingerprinting (RFLP analysis).
Once a potentially promising organism is detected, it is streaked onto rich media plates in order to obtain a pure culture (bright orange streaks are pure cultures).
We inoculate liquid cultures to grow the newly discovered bacteria to suitable cell mass so that the new natural product molecules can be extracted and analyzed for biological activity in anticancer and anti-infective tests.
The extracts often contain more than one compound, so when activity is found in an extract there is still more work to be done to isolate and characterize the natural product responsible for the activity. Professor Sherman and senior research fellow Jung Yeop Lee examine a column used for purification of extracts [pictured below]. Once a hit is identified, we work to purify the active fraction so we can obtain enough for structural characterization.
When the structure is solved, we work to identify and characterize the corresponding genetic blue print and biosynthetic enzymes responsible for assembly of the molecule. This can result in numerous fascinating research directions as a single project can provide years of work for a group of students, postdocs and visiting fellows.