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Drugs from Dirt

Researchers at the Rockefeller University have shown that the dirt beneath New York City teems with microbes that could prove useful in the fight against disease. In soil collected from city parks, the team dug up genetic evidence of bacteria capable of producing a wide range of compounds whose potent effects could potentially be harnessed for medicines.

“By sequencing and analyzing genes within soil samples, we found the genetic instructions for making a wide range of natural products that have the potential to become treatments for various conditions, from cancer to bacterial or fungal infections, or that are already being used as drugs,” says Sean Brady, head of Rockefeller’s Laboratory of Genetically Encoded Small Molecules. “The sheer diversity we saw suggests there are many more potentially valuable compounds out there awaiting discovery—even in a place as mundane as urban soil,” he adds.

Postdoctoral researcher Zachary Charlop-Powers examines DNA from soil samples that might encode microbial molecules with interesting properties. Image credit: Rockefeller University.Postdoctoral researcher Zachary Charlop-Powers examines DNA from soil samples that might encode microbial molecules with interesting properties. Image credit: Rockefeller University.In their battles against one another and other organisms, microbes have developed a wealth of chemical weapons that have been turned into medicines capable of myriad feats, from fighting off viruses to killing tumor cells. Because soil is crammed with competing microbes, it is a rich source of such microbe-derived medicines.

However, only a fraction of soil bacteria can be grown in the lab, severely limiting scientists’ ability to exploit them. Brady’s lab avoids this problem by looking directly at the bacterial DNA in soil. Within these sequences, the researchers can identify the instructions for making molecules that interest them.

The research on New York City soil drew on 275 samples from a variety of ecosystems within the city's park system. Students collected small amounts of topsoil, which were sent to Barnard College for isolation of their DNA and then to Rockefeller University, where scientists decoded the precise genetic sequences they contained. The researchers then compared their samples to those from known nonribosomal peptides and polyketides, two families of compounds to which many therapeutic molecules previously isolated from bacteria belong.

A single sample from Prospect Park in Brooklyn was found to harbor genes that likely encode 25 molecules that have been studied for potential use as antibiotics and other types of medicines. Similarly, a set of 11 representative compounds discovered elsewhere around the world—such as the antibiotic erythromycin from the Philippines and the antifungal agent natamycin from South Africa—were encoded by genes that were observed within the city parks’ soil.

The most important finding, say the scientists, is the abundance of unfamiliar genes.

“Less than 1% of molecule-encoding sequences matched up to the known genes to which we compared them,” says Zachary Charlop-Powers, postdoctoral researcher in Brady’s lab. “Similar efforts in soil collected elsewhere have also shown that novel molecule-encoding sequences vastly outnumber those we recognize. This suggests there are many as-yet-unidentified genes out there and, among these, some are likely to have potentially useful biological activity.”

For Brady, the genetic riches of city soil suggest it is time to shift the strategy for identifying new compounds.

“Throughout the history of the field, there has been this idea that one travels to remote parts of the world to collect strange bacteria. But those environments are fragile and disappearing,” he says. “Meanwhile, we’re finding that by using modern sequencing approaches, it’s possible to turn up all of the same potentially useful molecules in our own backyards.”

To contact the author of this article, email engineering360editors@ieeeglobalspec.com


Drugs from Dirt

Author : Internet   From : globalspec   Release times : 2018.01.16   Views : 114

Researchers at the Rockefeller University have shown that the dirt beneath New York City teems with microbes that could prove useful in the fight against disease. In soil collected from city parks, the team dug up genetic evidence of bacteria capable of producing a wide range of compounds whose potent effects could potentially be harnessed for medicines.

“By sequencing and analyzing genes within soil samples, we found the genetic instructions for making a wide range of natural products that have the potential to become treatments for various conditions, from cancer to bacterial or fungal infections, or that are already being used as drugs,” says Sean Brady, head of Rockefeller’s Laboratory of Genetically Encoded Small Molecules. “The sheer diversity we saw suggests there are many more potentially valuable compounds out there awaiting discovery—even in a place as mundane as urban soil,” he adds.

Postdoctoral researcher Zachary Charlop-Powers examines DNA from soil samples that might encode microbial molecules with interesting properties. Image credit: Rockefeller University.Postdoctoral researcher Zachary Charlop-Powers examines DNA from soil samples that might encode microbial molecules with interesting properties. Image credit: Rockefeller University.In their battles against one another and other organisms, microbes have developed a wealth of chemical weapons that have been turned into medicines capable of myriad feats, from fighting off viruses to killing tumor cells. Because soil is crammed with competing microbes, it is a rich source of such microbe-derived medicines.

However, only a fraction of soil bacteria can be grown in the lab, severely limiting scientists’ ability to exploit them. Brady’s lab avoids this problem by looking directly at the bacterial DNA in soil. Within these sequences, the researchers can identify the instructions for making molecules that interest them.

The research on New York City soil drew on 275 samples from a variety of ecosystems within the city's park system. Students collected small amounts of topsoil, which were sent to Barnard College for isolation of their DNA and then to Rockefeller University, where scientists decoded the precise genetic sequences they contained. The researchers then compared their samples to those from known nonribosomal peptides and polyketides, two families of compounds to which many therapeutic molecules previously isolated from bacteria belong.

A single sample from Prospect Park in Brooklyn was found to harbor genes that likely encode 25 molecules that have been studied for potential use as antibiotics and other types of medicines. Similarly, a set of 11 representative compounds discovered elsewhere around the world—such as the antibiotic erythromycin from the Philippines and the antifungal agent natamycin from South Africa—were encoded by genes that were observed within the city parks’ soil.

The most important finding, say the scientists, is the abundance of unfamiliar genes.

“Less than 1% of molecule-encoding sequences matched up to the known genes to which we compared them,” says Zachary Charlop-Powers, postdoctoral researcher in Brady’s lab. “Similar efforts in soil collected elsewhere have also shown that novel molecule-encoding sequences vastly outnumber those we recognize. This suggests there are many as-yet-unidentified genes out there and, among these, some are likely to have potentially useful biological activity.”

For Brady, the genetic riches of city soil suggest it is time to shift the strategy for identifying new compounds.

“Throughout the history of the field, there has been this idea that one travels to remote parts of the world to collect strange bacteria. But those environments are fragile and disappearing,” he says. “Meanwhile, we’re finding that by using modern sequencing approaches, it’s possible to turn up all of the same potentially useful molecules in our own backyards.”

To contact the author of this article, email engineering360editors@ieeeglobalspec.com


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