DIGGING FOR ANTIBIOTICS

Roger Linington knows firsthand how important antibiotics are to health.  They have helped him successfully recover from at least one critical infection. As the Canada Research Chair in Chemical Biology (High-Throughput Screening) Linington is on the hunt for a new class of antibiotics and he has some of the most powerful equipment in the world to help him.

Natural products extracted from mammals, bacteria, plants, microorganisms and marine life form the basis of approximately two-thirds of FDA approved drugs. Linington is convinced that there are more molecules with medicinal properties to be found.

His search has taken him from the jungles of Panama to the coral reefs of Hawaii to examine marine sediment, plants, invertebrates such as sponges and tunicates, and even porpoise guts for environmentally derived bacteria. Back in his lab, he catalogues the compounds and adds them to a comprehensive library of molecules that, once annotated, provides predictions of compound biological functions.

Linington explains the magnitude of his search.  “Typically, a gram of soil or ocean sediment can contain up to a billion bacterial cells, including tens of thousands of individual species. Any one of these species may harbour the genes required to biosynthesize the next antibiotic, or a treatment for other important diseases such as malaria or sleeping sickness.”

Linington is currently immersed in assembling a lab and a team that, once developed, will emerge as a state of the art facility for analytical chemistry in Canada. The lab is outfitted with a new suite of mass spectrometers that Linington says is an “amazing package of instrumentation that will bring substantial horsepower to our current ability to find and isolate molecules.”

These two mass spectrometry systems provide complementary perspectives on these complex mixtures. The first system, a Waters SYNAPT ion-mobility qTOF instrument, is capable of very high accuracy analysis of individual molecular species in natural products extracts. The second system, a Waters Autopurification system coupled to an SQD2 mass spectrometer, is designed for the rapid purification and characterization of individual constituents, providing complementary capacity to the SYNAPT instrument. Together with new software tools and biological assays being developed in house, these data will allow Linington’s team and collaborators to predict the modes of action of bioactive lead compounds against a wide variety of target diseases, from cancer cell targets to infectious disease agents.

Linington says, “The natural environment contains a staggering diversity of untapped biosynthetic capacity and the incredible analytical power available to us from the newest generation of mass spectrometers, is a game-changer. It is relatively easy to find molecules from Nature; finding molecules with value for human health problems is a much greater challenge, and one that requires new innovations in a range of areas including microbiology, analytical chemistry and chemical biology.”

Linington believes that “these new tools will revolutionize the discovery process and take it from a blind exercise in isolation chemistry, to an ordered, multiplexed approach.” Until recently, finding a molecule with antibiotic or anti-cancer properties have been exceptionally rare and a result of exceedingly labour intensive processes, but with new tools in hand, Linington hopes that his work will result in a serious contribution to finding new drugs. 

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