Creative Minds: Interpreting Your Genome

Artist's rendering of a doctor with a patient and a strand of DNA

Credit: Jane Ades, National Human Genome Research Institute, NIH

Just this year, we’ve reached the point where we can sequence an entire human genome for less than $1,000. That’s great news—and rather astounding, since the first human genome sequence (finished in 2003) cost an estimated $400,000,000!  Does that mean we’ll be able to use each person’s unique genetic blueprint to guide his or her health care from cradle to grave?  Maybe eventually, but it’s not quite as simple as it sounds.

Before we can use your genome to develop more personalized strategies for detecting, treating, and preventing disease, we need to be able to interpret the many variations that make your genome distinct from everybody else’s. While most of these variations are neither bad nor good, some raise the risk of particular diseases, and others serve to lower the risk. How do we figure out which is which?

Jay Shendure, an associate professor at the University of Washington in Seattle, has an audacious plan to figure this out, which is why he is among the 2013 recipients of the NIH Director’s Pioneer Award.

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MicroRNA Research Takes Aim at Cholesterol

Illustration of artery partially blocked by a cholesterol plaque

Caption: Illustration of artery partially blocked by a cholesterol plaque.

If you’re concerned about your cardiovascular health, you’re probably familiar with “good” and “bad” cholesterol: high-density lipoprotein (HDL) and its evil counterpart, low-density lipoprotein (LDL). Too much LDL floating around in your blood causes problems by sticking to the artery walls, narrowing the passage and raising risk of a stroke or heart attack. Statins work to lower LDL. HDL, on the other hand, cruises through your arteries scavenging excess cholesterol and returning it to the liver, where it’s broken down.

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Gain Without Pain: New Clues for Analgesic Design

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.

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Yeast Reveals New Drug Target for Parkinson’s

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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Less TOR Protein Extends Mouse Lifespan

Mouse walking towards a fountainThe average life expectancy in the United States currently is about 79 [1]. And, unsurprisingly, more than two-thirds of Americans say they’d like to live another 10 to 20 years longer [2].

One possible route to a longer life is to cut calories drastically. Not much fun perhaps, but there’s evidence it works in yeast, worms, and mice—but probably not in monkeys [3]. The potential life-extending strategy that I’d like to tell you about today focuses on the drug rapamycin, which blocks the activity of a protein called “target of rapamycin,” or TOR. Recently, a team here at NIH discovered that—at least in mice—reducing production of this protein through genetic engineering can add about 20% to the lifespan [4]. Continue reading