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Editor: Bijal Trivedi

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Sleep Gene Linked to Migraines

Oil painting of a woman holding her head, frowning

“Migraine.” This oil painting, by Dr. Emily Bates, was created while she was collecting data for this publication. As a migraine sufferer, this painting describes how migraines feel to her.
Credit: Emily Bates

Migraines—pounding headaches sometimes preceded by a visual “aura,” and often coupled with vomiting, nausea, distorted vision, and hypersensitivity to sound and touch—can be highly debilitating if recurrent and prolonged. They affect millions of Americans and an estimated 10–20 percent of the global population. Yet what predisposes individuals to them is somewhat of a mystery. Though there are certainly environmental triggers, the tendency for migraines to run in families suggests that there’s likely an inherited component. Recently, a team of NIH-funded researchers, one of whom regularly suffered from migraines herself, found a gene that plays a part. Continue reading “Sleep Gene Linked to Migraines” »

Exploiting Stem Cell Stickiness for Sorting

Photo of purple web-like objects adjacent to photo of a gloved hand holding a clear device with green lines, making it look like a circuit board.

Caption: Adult human fibroblast cells (left) are reprogramed into human induced pluripotent stem cells
(iPS cells). The iPS cells have a characteristic stickiness that lets them to adhere to sorting devices
(right) with different strengths than other cells.
Credit: Ankur Singh and Andres Garcia, Institute for Bioengineering & Bioscience, Georgia Tech

There is much excitement about the potential of stem cells for many applications, including regenerative medicine and treating human diseases. But growing pure cultures of stem cells by reprograming adult cells—like human fibroblasts—into a less differentiated cell type called a human induced Pluripotent Stem cell (iPS cell), is a tricky business. These stem cell cultures are often contaminated with other normal cells that do not have the same coveted therapeutic potential. Manually sorting these stem cells is time consuming and difficult; using chemical approaches can damage the DNA inside. Now, we have a better option: NIH funded researchers from the Georgia Institute of Technology in Atlanta have invented a cell-sorting device that exploits specific characteristics of iPS cells.

iPS cells have a characteristic ‘stickiness’ that allows them to adhere to surfaces inside the sorting chip with different strengths than other cells. This stickiness is due to a signature set of proteins on the surface of these stem cells. Normal cells are coated in other proteins that give their surfaces different adhesive properties.

The researchers say the method is gentle, efficient, rapid, and generates collections of stem cells that are 95–99% pure.

Reference:

Adhesion strength-based, label-free isolation of human pluripotent stem cells. Singh A, Suri S, Lee T, Chilton JM, Cooke MT, Chen W, Fu J, Stice SL, Lu H, McDevitt TC, García AJ. Nat Methods. 2013 May;10(5):438-44.

NIH support: National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke; National Cancer Institute

Fighting Malaria, With a Little Help from Bacteria

photo of a red-bellied mosquito adjacet to a photo of pink blobs

Caption: Anopheles female blood feeding and Plasmodium falciparum eggs in Anopheles mosquito midguts.
Credit: Image courtesy of Jose Luis Ramirez, Laboratory of Malaria and Vector Research, NIAID, NIH

It turns out that one of the most innovative and effective strategies to fight malaria might involve harnessing a bacterium called Wolbachia. This naturally occurring genus of bacteria infects many species of insects, including mosquitoes. The reason this is important is that Wolbachia-infected mosquitoes become resistant to the parasite Plasmodium falciparum, which causes some 219 million cases of malaria worldwide and more than 660,000 deaths [1]. Wouldn’t it be amazing if Wolbachia-infected mosquitoes blocked the transmission of malaria?

Unfortunately, Wolbachia don’t normally pass from generation to generation in Anopheles, the mosquitoes that spread malaria. But that hurdle has now been overcome. Continue reading “Fighting Malaria, With a Little Help from Bacteria” »

Fishing for Answers in Human Disease

Images of both a wild type zebrafish and a vhnf1 mutant zebrafish. The mutant fish shows abnormal bulging in its upper body.

Caption: Researcher Zhaoxia Sun, at Yale, uses the zebrafish to study Polycystic Kidney Disease, which affects more than 600,000 Americans. Mutations in the zebrafish vhnf1 gene, and its human counterpart, cause cysts in both zebrafish and human kidneys (as shown by the large “bubble” seen in the mutant fish). [3]
Credit: Zhoaxia Sun, Biological & Biomedical Sciences, Yale University

Wouldn’t it be instructive if we could see the effect of a genetic mutation in real time, as the gene was misbehaving? Well, that’s one of the perks of using the zebrafish—a tiny, striped, transparent fish.

Just last month, an international team of scientists—funded in part by NIH—published the entire genetic code of the zebrafish [1]. This is a vital resource for understanding human health and disease. How does the genetic blueprint of a fish help us or accelerate drug discovery? Well, it turns out that more than 75% of the genes that have been implicated in human diseases have counterparts in the zebrafish. So, if we discover a mutation in a human, we can make the corresponding mutation in the zebrafish gene—and often get a pretty good idea of how the gene works, how the mutation causes havoc, and how it causes disease in humans. We can even use the zebrafish to test potential drug candidates, to see whether they can alter or fix the symptoms before moving on to mice or humans.

Continue reading “Fishing for Answers in Human Disease” »

More Beta Cells, More Insulin, Less Diabetes

Artist redition of a liver, WAT fat, and BAT fat cells combining with green dots representing betatrophin combining to induce pancreatic cells

Caption: Betatrophin, a natural hormone produced in liver and fat cells, triggers the insulin-producing beta cells in the pancreas to replicate
Credit: Douglas Melton and Peng Yi

Type 2 diabetes (T2D) has arguably reached epidemic levels in this country; between 22 and 24 million people suffer from the disease. But now there’s an exciting new development: scientists at the Harvard Stem Cell Institute have discovered a hormone that might slow or stop the progression of diabetes [1].

T2D is the most common type of diabetes, accounting for about 95% of cases. The hallmark is high blood sugar. It is linked to obesity, which increases the body’s demand for more and more insulin. T2D develops when specific insulin-producing cells in the pancreas, called beta cells, become exhausted and can’t keep up with the increased demand. With insufficient insulin, blood glucose levels rise. Over time, these high levels of glucose can lead to heart disease, stroke, blindness, kidney disease, nerve damage, and even amputations. T2D can be helped by weight loss and exercise, but often oral medication or insulin shots are ultimately needed. Continue reading “More Beta Cells, More Insulin, Less Diabetes” »