Stories about: x-ray crystallography

Drawing a ring around antiviral immunity

Ubiquitin RIG-I innate antiviral immunity Sun Hur
Ubiquitin (pink ovals) doesn’t just tag proteins for recycling. It also may help keep our antiviral immune response in balance. (Image courtesy: Sun Hur)

If you follow cancer biology, then you’ve probably heard of ubiquitin before. Ubiquitin tags a cell’s damaged or used proteins and guides them to a cellular machine called the proteasome, which breaks them down and recycles their amino acids. Proteasome-blocking drugs like Velcade® that go after that recycling pathway in cancer cells have been very successful at treating two blood cancers—multiple myeloma and mantle cell lymphoma—and may hold promise for other cancers as well.

Less well known, however, is the fact that ubiquitin helps normal, healthy cells raise an alarm when viruses attack. Ubiquitin works with a protein called RIG-I, part of a complex signaling pathway that detects viral RNA and triggers an innate antiviral immune response.

Sun Hur, PhD, a structural biologist in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, has been studying RIG-I and other members of the innate cellular antiviral response for some time. And in a recent paper in Nature, she provided a structural rationale for how ubiquitin helps RIG-I do its job, and how that might help keep our immune system from getting out of hand.

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A picture is worth a thousand words for understating innate immunity

What you’re looking at is one of the key ways in which our immune system recognizes viruses before they cause trouble: by sensing the physical presence of their genes. This image by Sun Hur, PhD, will help us better understand how.

Our immune system has immense powers of observation. It needs to in order to fend off the millions of bacteria, viruses, fungi, you name it, that we get exposed to every day.

I’m not talking about antibodies and T cells—parts of the immune system’s adaptive arm, which is fine-tuned to recognize a specific virus or bacterium. Rather, I’m talking about pattern recognition proteins—biological sensors capable of recognizing features and structures that only bacteria or viruses have. These make up the immune system’s innate arm, which essentially primes the body to attack anything that looks remotely like it doesn’t belong.

For instance, our cells carry sensors that can detect double-stranded RNA (dsRNA), which certain kinds of viruses use to encode their genome—like the rotavirus, which causes severe diarrhea in infants and small children. Our genome, by contrast, is encoded in DNA, and the RNA we make is single-stranded; if there’s dsRNA present, it means there’s a virus around.

In a recent paper in Cell, Sun Hur, PhD, of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, and one of her postdoctoral fellows, Bin Wu, PhD, spotlight one of our dsRNA pattern recognizers, a protein called MDA5.

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Moving in on what makes malaria move

The exceedingly complex life cycle of malaria. Within it lies the key to developing a vaccine against the parasite. (CDC)

The malaria parasite (or parasites: four species of Plasmodium can cause malaria in people) has a really complex life cycle.  That complexity has allowed this mosquito-borne parasite from bringing untold misery to the human race for millennia. The World Health Organization thinks it causes 216 million cases of disease every year, while the U.S. Centers for Disease Control and Prevention estimates that some 3.3 billion people live at risk of malaria infection around the globe. Even in the United States, where malaria was officially eradicated 60 years ago, there are still about 1,500 cases every year.

All these numbers add up to one fact: we need a vaccine, badly. This is where malaria’s complexity becomes a problem.

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The shape of things to come

Detailed image of a bacterial enzyme used to degrade a major organic pollutant.

Imagine you’re a long-suffering biologist, and imagine that the problem is figuring out the three-dimensional shape of a very important molecule. The solution could lead to (a) new insights into disease and potential therapies, and (b) career advancement. What if someone gave you virtually unlimited computer power that could crack the problem you’re trying to solve overnight?

team at Children’s Hospital Boston has created a super-charged way of solving molecule shapes, harnessing idle scientific computer time across the country and around the world to survey vast reference databases – a “Google Shape” if you will.

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