Wednesday, June 24, 2015

Drug Discovery in your Backyard


Fig.1. Example plates of fungi being isolated from soil samples in the Natural Products Discovery Group citizen science project at the University of Oklahoma (Credit: Candace Coker, University of Oklahoma).

Editor’s Note: For the second article in our International Year of Soils series, learn about how to find the next generation of medicine in your own backyard!


In 1928, Alexander Fleming returned from holiday to find something amazing growing on his Petri dishes. Once full of Staphylococcus bacteria, it was now growing mold. Secretions from this mold, later identified as Penicillium notatum, proved to kill a host of harmful bacteria and became the first true antibiotic. Robert Cichewicz, a professor of chemistry and biochemistry at the University of Oklahoma, would classify Fleming’s bacteria-killing compounds as natural products, a term applied to many types of compounds made by cells, but are not necessary for their survival like essential proteins or lipids.

“Some are used for defense, some of them are used for signaling, some of them are used for who knows what at this point,” he said.


Fig.2. Soil sample being prepared for plating on fungi-specific growth media at the University of Oklahoma (Credit: Candace Coker, University of Oklahoma)

Quantifying the Unknown

Cichewicz and his lab, the Natural Products Discovery Group (NPDG), are out to investigate how and why natural products are made and in the process, discover new hiding places for pharmaceutical drugs. Roughly half of approved drugs today were found in nature, whether from fungi, like penicillin, or plants, like the antimalarial quinine. The less-studied area of natural products from terrestrial fungi appealed to Cichewicz.

“It’s estimated that there’s several million fungi in the world, yet somewhere on the order of a hundred thousand or more have ever been studied,” Cichewicz said.

So how do you harvest possibly life-saving compounds from unidentified fungi in nature?

The NPDG isolates fungi from soil samples sent in from around the country. Soil is the new frontier for medicine, offering a wide array of diverse microorganisms, many of which are unknown. Once fungal strains are isolated from samples using fungal-specific growth media, researchers analyze them for natural products, which might inhibit different diseases. Each sample is a new possibility for drug discovery.

This entire process, from soil to chemical compound, can take up to two years. Once ready for pharmaceutical drug development, another two decades may pass before the medicine hits the market. The length of time, however, does not stop the scientist.

“We are the first step, we are the discovery step! The entire timeline is just laid out before us,” Cichewicz said. “It’s kind of daunting [...] but it’s also this investment that somebody, somewhere has got to make, and I think we have the right tools to do so.”


Fig.3. The soil sample on the left (personally sent in by this intrepid citizen scientist-author) might have fungus that will end up in the tube on the right for extraction and testing in the NPDG lab (Credit: Adele Crane [left] and Candace Coker, University of Oklahoma [right]).

Going Viral with Fungi

Such a lengthy process needs to begin somewhere. Although NPDG started off extremely self-reliant on its own soil collection activities, Cichewicz quickly realized he needed a better plan to get a higher quantity of geographically diverse samples.

Out of this problem came the idea for citizen science: people could send in samples of soil and the lab could study the unique and often novel fungi. Though not a guarantee when harnessing citizen science, nearly every sample NPDG receives has some fungi for investigation.

“On average, we get 10 to 11 different fungal isolates from each soil sample, and that number can go up to over a hundred in certain unique soil samples,” Cichewicz said.

The presence of fungi was not the surprising factor, but rather the passion of the citizen scientists involved. A viral post on Reddit about NPDG catapulted sample kit requests from 500 a year ago to an astounding 7,000 in a 3 month period just this year. While the social media success of this project strains the NPDG’s ability to fund the project, it also creates an awareness about the importance of natural products in soil.

“We’re looking to keep the program going at the level that we see it moving towards, which is fabulous. We don’t want to in any way slow down,” Cichewicz said.

This project walks the line between public outreach and biomedical research. Interest in soil, science, or even specific medicines often spurs participation in the citizen science project, but NPDG needs outside funding to sustain the effort. Cichewicz ultimately hopes to give back to the individuals, students, and researchers who have sent in their soil. His lab is currently developing an online tool to display information about each sample.

“We don’t want this to be a one-way street [...] We’re working right now on photo-documenting every plate of fungi that comes out of the program,” he said.


Fig.4. Flasks of fungi growing for testing in the NPDG lab (Credit: Candace Coker, University of Oklahoma).

Collecting for the Future

Despite funding challenges, the project’s popularity promises the potential for new discoveries in previously unexplored environments and ecological niches. So far, Cichewicz and his lab have already found strains that fit into new orders and possibly even new classes of fungi.

“That’s some pretty phenomenal, deep diversity we’re talking about when you think about all the fungi that have been looked at,” said Cichewicz.

Then again, there are millions of fungi to go, which means more opportunity to understand biodiversity at a deep, geographical level. Such biodiversity must be preserved, so Cichewicz keeps fungi found in soil samples. His culture collection, safely kept at a cool -80°C for later recovery, is made up of more than 10,000 fungal isolates. The huge increase in soil samples thanks to Reddit might push that number closer to 60,000. Cichewicz wants this repository to be a resource for people beyond University of Oklahoma walls.

“We can’t cover all the biomedical needs in the world, so wouldn’t it be great if this library were available for other people to screen? I see this as a tremendous resource that could have great benefit and value to the research community, as well as a drug discovery tool,” Cichewicz said.

He looks forward to sharing this repository with other research groups, and expanding the impact of this extraordinary collection. NPDG and other efforts that address antibiotic resistance are essential for the future of public health. So send in your soil. You never know if the mold in your backyard will hold the next antibiotic.

To learn more about how your soil might make a difference, check out the Natural Products Discovery Group webpage. If you are interested in participating in their citizen science project, you can request a free soil collection kit here.



References:

Aldridge, S., Parascandola, J., Sturchio, J.L. (1999). Discovery and Development of Penicillin: International Historic Chemical Landmark. American Chemical Society and the Royal Society of Chemistry. Retrieved from http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html.

Natural Products Discovery Group, University of Oklahoma. (2014). Fungal Natural Products Discovery Process. Retrieved from http://npdg.ou.edu/Websites/npdg/images/CS_Discovery_Pipeline_s.pdf.

Veeresham, C. (2012). Natural products derived from plants as a source of drugs. J Adv Pharm Technol Res., 3: 200-201. doi: 10.4103/2231-4040.104709.




Glossary

natural products
A compound produced by an organism or groups of organisms found in nature.
growth media
A gel or liquid which supports the growth of microorganisms. The composition of the media - in essence, food - promotes the growth of only certain microorganisms thereby isolating them for study.
culture collection
A repository of strains of microorganisms, which preserve microbial biodiversity and can provide material for research on particular strains.

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