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Copying and Reading the Book of Life Inside One Cell, Accurately

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Microwell strip

Caption: The genome researchers collaborated with materials science engineers to create the arrays of microwells or compartments that each capture a single cell.
Credit: UC San Diego Jacobs School of Engineering

Decoding the complete DNA genome in a single cell has been a major goal of technology developers. But the methods aren’t quite able to deal with that yet.  So, for scientists to do this, they first need to make multiple copies of the DNA inside. Until now, the copying technology hasn’t been as accurate as scientists would like. If you think of the genome like a book, then our current copiers replicate certain chapters thousands of times, others just a few, and some not at all. As you can imagine, if you tried to read one of these copies, you’d be quite confused—and you certainly couldn’t rely on your reading for any medical purposes.

Now, NIH-funded researchers at the University of California, San Diego, have developed a new molecular technique that can accurately and uniformly copy the DNA inside a single cell [1]. Using this technique, they’ve already made some surprising discoveries.


Snapshots of Life: Amyloid Glows in Polarized Light

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Amyloidosis as seen under a microscope

Credit: William Lewis, Emory University School of Medicine, Atlanta

While this may look like one of those bold canvases from the brush of an Abstract Expressionist, it’s actually a close-up of the biology underlying a rare, but relentless, group of conditions known as amyloidosis. This winner of the Federation of American Societies for Experimental Biology’s 2013 BioArt contest traces in exquisite detail the damage that amyloid, which is the abnormal accumulation of specific extracellular proteins, can inflict on the heart.


Fighting Obesity: New Hopes From Brown Fat

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Artist rendition of a xray showing brown fat as glowing green

Caption: Brown fat—actually marked in green on this image—is wrapped around the neck and shoulders. This “shawl” of brown fat warms blood before it travels to the brain.
Illustration: John MacNeill, based on patient imaging software designed by Ilan Tal. Copyright 2011 Joslin Diabetes Center

If you want to lose weight, then you actually want more fat, not less. But you need the right kind: brown fat. This special type of fatty tissue burns calories, puts out heat like a furnace, and helps to keep you trim. White fat, on the other hand, stores extra calories and makes you, well, fat. Wouldn’t it be nice if we could instruct our bodies to make more brown fat, and less white fat? Well, NIH-funded researchers have just taken another step in that direction [1].


Gain Without Pain: New Clues for Analgesic Design

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A mouse and a scorpion sharing a space and facing nose-to-nose.

Photo Credit: Matthew Rowe, Michigan State University

If you’re a southern grasshopper mouse, nothing beats a delicious snack of scorpion. But what, you might ask, prevents that from being a painful or even fatal event?  Well, this native of the Arizona desert has evolved an amazing resistance to the stings of the bark scorpion—stings so painful and toxic they kill house mice and other rodents of similar size.

Why am I sharing this bit of natural history? Well, it turns out that by studying the grasshopper mouse and its unusual diet, NIH-funded researchers at the Indiana University School of Medicine and collaborators at the University of Texas, Austin, have identified a new target on nerve fibers that could lead to more effective and less addictive pain medications for humans.


Yeast Reveals New Drug Target for Parkinson’s

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Untreated yeast shows clumps of brightly colored spots, while treated yeast are more even in their color.

Caption: Left, yeast sick with too much α-synuclein, a protein that is implicated in Parkinson’s disease. Right, the same yeast cells after a dose of NAB, which seems to reverse the toxic effects of α-synuclein.
Credit: Daniel Tardiff, Whitehead Institute

Many progressive neurodegenerative disorders like Alzheimer’s, Huntington’s, and Parkinson’s disease, are characterized by abnormal clumps of proteins that clog up the cell and disrupt normal cellular functions. But it’s difficult to study these complex disease processes directly in the brain—so NIH-funded researchers, led by a team at the Whitehead Institute for Biomedical Research, Cambridge, MA, have turned to yeast for help.

Now, it may sound odd to study a brain disease in yeast, a microorganism long used in baking and brewing. After all, the brain is made up of billions of cells of many different types, while yeast grows as a single cell. But because the processes of protein production are generally conserved from yeast to humans, we can use this infinitely simpler organism to figure out what the proteins clumps are doing and test various drug candidates to halt the damage.


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