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Variations within neurons

Caption: Single-cell analysis helps to reveal subtle, but important, differences among human cells, including many types of brain cells.
Credit: Shutterstock, modified by Ryan M. Mulqueen

Imagine how long it would take to analyze the 37 trillion or so cells that make up the human body if you had to do it by hand, one by one! Still, single-cell analysis is crucial to gaining a comprehensive understanding of our biology. The cell is the unit of life for all organisms, and all cells are certainly not the same. Think about it: even though each cell contains the same DNA, some make up your skin while others build your bones; some of your cells might be super healthy while others could be headed down the road to cancer or Alzheimer’s disease.

So, it’s no surprise that many NIH-funded researchers are hard at work in the rapidly emerging field known as single-cell analysis. In fact, one team recently reported impressive progress in improving the speed and efficiency of a method to analyze certain epigenetic features of individual cells [1]. Epigenetics refers to a multitude of chemical and protein “marks” on a cell’s DNA—patterns that vary among cells and help to determine which genes are switched on or off. That plays a major role in defining cellular identity as a skin cell, liver cell, or pancreatic cancer cell.

The team’s rather simple but ingenious approach relies on attaching a unique combination of two DNA barcodes to each cell prior to analyzing epigenetic marks all across the genome, making it possible for researchers to pool hundreds of cells without losing track of each of them individually. Using this approach, the researchers could profile thousands of individual cells simultaneously for less than 50 cents per cell, a 50- to 100-fold drop in price. The new approach promises to yield important insights into the role of epigenetic factors in our health, from the way neurons in our brains function to whether or not a cancer responds to treatment.

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Credit: Wellcome Centre for Human Neuroimaging, University College London.

In recent years, researchers fueled by the BRAIN Initiative and many other NIH-supported efforts have made remarkable progress in mapping the human brain in all its amazing complexity. Now, a powerful new imaging technology promises to further transform our understanding [1]. This wearable scanner, for the first time, enables researchers to track neural activity in people in real-time as they do ordinary things—be it drinking tea, typing on a keyboard, talking to a friend, or even playing paddle ball.

This new so-called magnetoencephalography (MEG) brain scanner, which looks like a futuristic cross between a helmet and a hockey mask, is equipped with specialized “quantum” sensors. When placed directly on the scalp surface, these new MEG scanners can detect weak magnetic fields generated by electrical activity in the brain. While current brain scanners weigh in at nearly 1,000 pounds and require people to come to a special facility and remain absolutely still, the new system weighs less than 2 pounds and is capable of generating 3D images even when a person is making motions.

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MEMOIR cells

Caption: MEMOIR cells variably activate (cyan). The recorded information is then read out to visualize certain RNA transcripts (red).
Credit: Elowitz and Cai Labs, Caltech, Pasadena, CA

One of the most fascinating challenges in biology is understanding how a single cell divides and differentiates to form a complex, multicellular organism. Scientists can learn a lot about this process by tracking time-lapse images through a microscope. But gazing through a lens has its limitations, especially in the brain and other opaque and inaccessible tissues and organs.

With support from a 2017 NIH Director’s Transformative Research Program, a California Institute of Technology (Caltech) team now has a way around this problem. Rather than watching or digging information out of cells, the team has learned how to program cells to write their own molecular memoirs. These cells store the information right in their own genomic hard drives. Even better, that information is barcoded, allowing researchers to read it out of the cells without dissecting tissue. The programming can be performed in many different cell types, including stem or adult cells in tissues throughout the body.

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Benchtop Centrifuge

Credit: National Institute of Allergy and Infectious Diseases, NIH

A major part of NIH’s mission is to support basic research that generates fundamental knowledge about the nature and behavior of living systems. Such knowledge serves as the foundation for the biomedical advances needed to protect and improve our health—and the health of generations to come.

Of course, it’s often hard to predict how this kind of basic research might benefit human populations, and the lag time between discovery and medical application (if that happens at all) can be quite long. Some might argue, therefore, that basic research is not a good use of funds, and all of NIH’s support should go to specific disease targets.

To counter that perception, I’m pleased to share some new findings that underscore the importance of publicly supported basic research. In an analysis of more than 28 million papers in the PubMed.gov database, researchers found NIH contributed to published research that was associated with every single one of the 210 new drugs approved by the Food and Drug Administration from 2010 through 2016 [1]. More than 90 percent of that contributory research was basic—that is, related to the discovery of fundamental biological mechanisms, rather than actual development of the drugs themselves.

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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 City

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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