Powerful Antibiotics Found in Dirt

Dirt

Caption: Researchers found a new class of antibiotics in a collection of about 2,000 soil samples.
Credit: Sean Brady, The Rockefeller University, New York

Many of us think of soil as lifeless dirt. But, in fact, soil is teeming with a rich array of life: microbial life. And some of those tiny, dirt-dwelling microorganisms—bacteria that produce antibiotic compounds that are highly toxic to other bacteria—may provide us with valuable leads for developing the new drugs we so urgently need to fight antibiotic-resistant infections.

Recently, NIH-funded researchers discovered a new class of antibiotics, called malacidins, by analyzing the DNA of the bacteria living in more than 2,000 soil samples, including many sent by citizen scientists living all across the United States [1]. While more work is needed before malacidins can be tried in humans, the compounds successfully killed several types of multidrug-resistant bacteria in laboratory tests. Most impressive was the ability of malacadins to wipe out methicillin-resistant Staphylococcus aureus (MRSA) skin infections in rats. Often referred to as a “super bug,” MRSA threatens the lives of tens of thousands of Americans each year [2].

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Sequencing Human Genome with Pocket-Sized “Nanopore” Device

MinION sequencing device

Caption: MinION sequencing device plugged into a laptop/Oxford Nanopore Technologies

It’s hard to believe, but it’s been almost 15 years since we successfully completed the Human Genome Project, ahead of schedule and under budget. I was proud to stand with my international colleagues in a celebration at the Library of Congress on April 14, 2003 (which happens to be my birthday), to announce that we had stitched together the very first reference sequence of the human genome at a total cost of about $400 million. As remarkable as that achievement was, it was just the beginning of our ongoing effort to understand the human genome, and to use that understanding to improve human health.

That first reference human genome was sequenced using automated machines that were the size of small phone booths.  Since then, breathtaking progress has been made in developing innovative technologies that have made DNA sequencing far easier, faster, and more affordable. Now, a report in Nature Biotechnology highlights the latest advance: the sequencing and assembly of a human genome using a pocket-sized device [1]. It was generated using several “nanopore” devices that can be purchased online with a “starter kit” for just $1,000. In fact, this new genome sequence—completed in a matter of weeks—includes some notoriously hard-to-sequence stretches of DNA, filling several key gaps in our original reference genome.

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Adding Letters to the DNA Alphabet

semi-synthetic bacterium

Credit: William B. Kiosses

The recipes for life, going back billions of years to the earliest single-celled organisms, are encoded in a DNA alphabet of just four letters. But is four as high as the DNA code can go? Or, as researchers have long wondered, is it chemically and biologically possible to expand the DNA code by a couple of letters?

A team of NIH-funded researchers is now answering these provocative questions. The researchers recently engineered a semi-synthetic bacterium containing DNA with six letters, including two extra nucleotides [1, 2]. Now, in a report published in Nature, they’ve taken the next critical step [3]. They show that bacteria, like those in the photo, are not only capable of reliably passing on to the next generation a DNA code of six letters, they can use that expanded genetic information to produce novel proteins unlike any found in nature.

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Creative Minds: A New Way to Look at Cancer

Bradley Bernstein

Bradley Bernstein

Inside our cells, strands of DNA wrap around spool-like histone proteins to form a DNA-histone complex called chromatin. Bradley Bernstein, a pathologist at Massachusetts General Hospital, Harvard University, and Broad Institute, has always been fascinated by this process. What interests him is the fact that an approximately 6-foot-long strand of DNA can be folded and packed into orderly chromatin structures inside a cell nucleus that’s just 0.0002 inch wide.

Bernstein’s fascination with DNA packaging led to the recent major discovery that, when chromatin misfolds in brain cells, it can activate a gene associated with the cancer glioma [1]. This suggested a new cancer-causing mechanism that does not require specific DNA mutations. Now, with a 2016 NIH Director’s Pioneer Award, Bernstein is taking a closer look at how misfolded and unstable chromatin can drive tumor formation, and what that means for treating cancer.

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Studies of Dogs, Mice, and People Provide Clues to OCD

OCD

Thinkstock/wildpixel

Chances are you know someone with obsessive-compulsive disorder (OCD). It’s estimated that more than 2 million Americans struggle with this mental health condition, characterized by unwanted recurring thoughts and/or repetitive behaviors, such as excessive hand washing or constant counting of objects. While we know that OCD tends to run in families, it’s been frustratingly difficult to identify specific genes that influence OCD risk.

Now, an international research team, partly funded by NIH, has made progress thanks to an innovative genomic approach involving dogs, mice, and people. The strategy allowed them to uncover four genes involved in OCD that turn out to play a role in synapses, where nerve impulses are transmitted between neurons in the brain. While more research is needed to confirm the findings and better understand the molecular mechanisms of OCD, these findings offer important new leads that could point the way to more effective treatments.

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